KR20060066139A - 결핵의 면역치료 및 진단용 화합물과 이의 사용 방법 - Google Patents
결핵의 면역치료 및 진단용 화합물과 이의 사용 방법 Download PDFInfo
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- KR20060066139A KR20060066139A KR1020067010257A KR20067010257A KR20060066139A KR 20060066139 A KR20060066139 A KR 20060066139A KR 1020067010257 A KR1020067010257 A KR 1020067010257A KR 20067010257 A KR20067010257 A KR 20067010257A KR 20060066139 A KR20060066139 A KR 20060066139A
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Abstract
본 발명은 결핵에 대한 예방 면역성을 유도하기 위한 화합물 및 방법에 관한 것이다. 본 발명의 화합물은 1종 이상의 엠. 투베르쿨로시스(M. tuberculosis) 단백질의 하나 이상의 면역원성 부분을 포함하는 폴리펩티드 및 이 폴리펩티드를 코딩하는 DNA 분자를 포함한다. 이러한 화합물은 엠. 투베르쿨로시스 감염에 대한 면역화용 백신 및/또는 약학 조성물로 제형화될 수 있으며, 또한 결핵을 진단하는 데 사용될 수 있다.
결핵
Description
도 1a 및 도 1b는 재조합 ORF-2 및 ORF-2에 대한 합성 펩티드에 의한, 제1 PPD 양성 공여체(이하 D7로 칭함)로부터 유도된 T 세포에서의 증식 및 인터페론-γ 생성의 자극을 각각 보여준다.
도 2a 및 도 2b는 재조합 ORF-2 및 ORF-2에 대한 합성 펩티드에 의한, 제2 PPD 양성 공여체(이하 D160으로 칭함)로부터 유도된 T 세포에서의 증식 및 인터페론-γ 생성의 자극을 각각 보여준다.
본 발명은 일반적으로 마이코박테리움 투베르쿨로시스(Mycobacterium tuberculosis) 감염을 검출, 치료 및 예방하는 방법에 관한 것이다. 더욱 구체적으로 본 발명은 마이코박테리움 투베르쿨로시스 항원, 또는 이의 일부 또는 기타 변형체를 포함하는 폴리펩티드와, 마이코박테리움 투베르쿨로시스 감염에 대한 진단 및 백신 접종에 사용하기 위한 폴리펩티드의 용도에 관한 것이다.
결핵은 일반적으로 마이코박테리움 투베르쿨로시스에 감염되어 유발되는 만 성 감염성 질병이다. 결핵은 개발도상국에서 주요 질병일 뿐 아니라 전세계 선진국에서도 그 문제성이 증가하고 있으며, 매년 약 8백만건의 신규 사례가 발생하여 3백만명이 사망한다. 감염이 되어도 상당한 기간 동안 증상이 없을 수 있지만, 가장 일반적으로는 이 질병은 폐의 급성 염증을 보이며 열과 비생산적인 기침을 유발시킨다. 치료하지 않고 그대로 방치하면, 심각한 합병증을 초래하고 일반적으로는 사망하게 된다.
결핵은 일반적으로 장기간에 걸친 항생제 치료법을 이용하여 제어할 수 있지만, 이러한 치료는 질병이 유포되는 것을 막기에는 충분하지 않다. 감염된 개체는 무증상일 수 있지만, 때로는 전염성이 있다. 또한, 치료법에 순응하는 것이 중요하지만, 환자의 행동 방식을 감시하기는 어렵다. 일부 환자는 전 치료 과정을 종결짓지 못하는데, 이렇게 되면 치료 효과가 없으며, 내약제성이 유발될 수 있다.
결핵이 만연되는 것을 억제하는 데에는 효과적인 백신 접종과 질병의 정확한 조기 진단이 필요하다. 현재, 생박테리아로 백신 접종하는 것이 예방 면역을 유도하는 가장 효과적인 방법이다. 이러한 용도로 사용되는 가장 일반적인 마이코박테리움은 마이코박테리움 보비스(Mycobacterium bovis)의 무독성 균주인 바실러스 칼메트-구에린(BCG: Baccillus Calmette-Guerin)이다. 그러나, BCG의 안전성 및 효능은 논쟁의 대상이 되고 있어서, 미국 등의 일부 국가에서는 일반 대중에게 이 백신을 접종하지 않는다. 진단은 보통, 투베르쿨린 PPD(단백질 정제된 유도체)를 피내에 노출시키는 피부 테스트를 이용하여 행한다. 항원 특이적 T 세포 반응으로 인해 주사한 지 48∼72 시간 후 주사 부위에 측정가능한 경결이 생기는데, 이 경결은 마 이코박테리아의 항원에 노출되었음을 의미한다. 그러나, 이 테스트 방법의 문제점은 민감성 및 특이성이며, BCG를 접종한 개체를 감염된 개체와 구별할 수가 없다.
대식세포는 엠. 투베르쿨로시스 면역성의 기본 효과기로서 작용하는 것으로 확인되었으며, T 세포는 이러한 면역성의 주요 유도자이다. 엠. 투베르쿨로시스 감염에 대한 보호에 있어서 T 세포가 필수적인 역할을 한다는 것은, 인간 면역결핍 바이러스(HIV) 감염과 관련이 있는 CD4 T 세포의 고갈로 인해 AIDS 환자에서 엠. 투베르쿨로시스가 자주 발생한다는 것으로 알 수 있다. 마이코박테리움 반응성 CD4 T 세포는 감마 인터페론(IFN-γ)의 유효한 생산자인 것으로 확인되었으며, 또한 IFN-γ는 마우스에서 대식세포의 마이코박테리아 억제 효과를 촉발하는 것으로 확인되었다. 인간에서 IFN-γ의 역할은 마우스에서보다는 덜 명확하지만, 여러 연구로부터 1,25-디히드록시-비타민 D3가, 단독으로 또는 IFN-γ또는 종양 괴사 인자-알파와 함께, 인간 대식세포를 활성화시켜 엠. 투베르쿨로시스 감염을 억제한다는 것이 확인되었다. 또한, IFN-γ는 인간 대식세포가 1,25-디히드록시-비타민 D3을 생성하도록 자극하는 것으로 알려져 있다. 유사하게, IL-12는 엠. 투베르쿨로시스 감염에 대한 내성을 자극하는 역할을 하는 것으로 확인되었다. 엠. 투베르쿨로시스 감염의 면역학에 대해서는 Chan 및 Kaufmann 등의 문헌[Tuberculosis: Pathogenesis, Protection and Control, Bloom (ed.), ASM Press, 1994년 워싱톤 DC]을 참조할 수 있다.
따라서, 결핵을 예방, 치료 및 검출하기 위한 개선된 백신 및 방법이 당업계에 필요하다. 본 발명은 이러한 요구를 만족시키고 나아가 관련된 다른 장점들을 제공한다.
간단히 설명하면, 본 발명은 결핵의 예방 및 진단을 위한 화합물 및 방법을 제공한다. 제1 양태에서, 본 발명은 엠. 투베르쿨로시스 항원의 면역원성 부분, 또는 단지 보존적 치환 및/또는 변형에 있어서만 상이한 상기 항원의 변형체를 포함하는 폴리펩티드를 제공하는데, 상기 항원은 서열 번호 1, 11, 12, 83, 103-108, 125, 127, 129-137, 139 및 140에 개시된 서열, 이 서열의 상보 서열, 및 서열 번호 1, 11, 12, 83, 103-108, 125, 127, 129-137, 139 및 140에 개시된 서열 또는 이의 상보 서열에 보통의 엄중 조건하에서 하이브리드화하는 DNA 서열로 구성된 군에서 선택되는 DNA 서열에 의해 코딩되는 아미노산 서열을 포함한다. 제2 양태에서, 본 발명은 서열 번호 16-33, 109, 126, 138, 141, 142에 제공된 서열 및 이의 변형체로 구성된 군에서 선택되는 아미노산 서열을 갖는 엠. 투베르쿨로시스 항원의 면역원성 부분을 포함하는 폴리펩티드를 제공한다.
관련 제3 양태에서, 전술한 폴리펩티드를 코딩하는 DNA 서열, 이들 DNA 서열을 포함하는 발현 벡터 및 이러한 발현 벡터로 형질전환되거나 또는 형질감염된 숙주 세포를 제공한다.
제4 양태에서, 본 발명은 본 발명의 제1 폴리펩티드 및 제2 폴리펩티드를 포함하는 융합 단백질, 또는 대안적으로 본 발명의 폴리펩티드 및 공지된 엠. 투베르쿨로시스 항원을 포함하는 융합 단백질을 제공한다.
제5 양태에서, 본 발명은 1종 이상의 상기 폴리펩티드, 또는 이러한 폴리펩 티드를 코딩하는 DNA 분자, 및 생리적 허용 담체를 포함하는 약학 조성물을 제공한다. 또한, 본 발명은 전술한 1종 이상의 폴리펩티드 및 비특이적인 면역 반응 인핸서를 함유하는 백신을, 이러한 폴리펩티드를 코딩하는 1종 이상의 DNA 서열 및 비특이적 면역 반응 인핸서를 함유하는 백신과 함께 제공한다.
제6 양태에서, 본 발명은 1종 이상의 상기 폴리펩티드의 유효량을 환자에게 투여하는 단계를 포함하여 환자의 예방 면역성을 유도하는 방법을 제공한다.
본 발명의 제7 양태에서, 환자의 결핵을 검출하기 위한 방법 및 진단 키트를 제공한다. 이 방법은 상기 1종 이상의 폴리펩티드와 환자의 피부 세포를 접촉시키는 단계 및 환자의 피부상에서의 면역 반응을 검출하는 단계를 포함한다. 진단 키트는 1종 이상의 상기 폴리펩티드와 함께 환자의 피부 세포와 폴리펩티드를 접촉시키기에 충분한 장치를 포함한다.
제8 양태에서, 본 발명은 환자의 결핵을 검출하기 위한 방법을 제공하는데, 이 방법은 서열 번호 2-10, 102, 128에 개시된 서열, 이 서열의 상보 서열 및 서열 번호 2-10, 102, 128에 개시된 서열에 하이브리드화하는 DNA 서열로 구성된 군에서 선택되는 DNA 서열에 의해 코딩되는 1종 이상의 폴리펩티드와 환자의 피부 세포를 접촉시키는 단계; 및 환자의 피부에서의 면역 반응을 검출하는 단계를 포함한다. 이러한 방법에 사용하기 위한 진단 키트도 제공된다.
본 발명의 이들 양태 및 기타 양태는 후술하는 발명의 상세한 설명 및 첨부 도면을 참조하면 분명해질 것이다. 본원에서 언급한 모든 문헌은 그 전문을 본원에서 참고로 인용하였다.
전술한 바와 같이, 본 발명은 일반적으로 결핵을 예방, 치료 및 진단하기 위한 조성물 및 방법에 관한 것이다. 본 발명의 조성물은 엠. 투베르쿨로시스 항원의 하나 이상의 면역원성 부분 또는 단지 보존적 치환 및/또는 변형에 있어서만 차이가 있는 상기 항원의 변형체를 포함하는 폴리펩티드를 함유한다. 본원에서 사용된 "폴리펩티드"란 용어는 아미노산 잔기가 펩티드 공유결합에 의해 결합되어 있는 전길이의 단백질을 비롯한 임의 길이의 아미노산쇄(즉, 항원)를 포함하는 개념이다. 따라서, 상기 항원중 하나의 면역원성 부분을 포함하는 폴리펩티드는 면역원성 부분으로만 구성되거나 또는 추가 서열을 포함할 수 있다. 추가 서열은 천연의 엠. 투베르쿨로시스 항원에서 유래한 것이거나 또는 이종성일 수 있고, 이러한 서열은 면역원성일 수 있다(그러나, 필수 요건은 아님).
본원에서 사용된 "면역원성"이란 환자, 예컨대 인간 및/또는 생물학적 시료에서 면역 반응(예컨대, 세포성 면역 반응)을 유도하는 능력을 말한다. 구체적으로, 면역원성인 항원(및 이러한 항원의 면역원성 부분 또는 기타 변형체)은 T 세포, NK 세포, B 세포 및 대식세포로 이루어진 군에서 선택되는 하나 이상의 세포(이들 세포는 엠. 투베르쿨로시스 면역 개체로부터 유래함)를 포함하는 생물학적 시료중에서 세포 증식, 인터루킨-12 생성 및/또는 인터페론-γ생성을 자극할 수 있다. 1종 이상의 엠. 투베르쿨로시스 항원의 하나 이상의 면역원성 부분을 포함하는 폴리펩티드는 일반적으로 환자에서 결핵을 검출하거나 또는 결핵에 대한 예방 면역을 유도하는 데 사용할 수 있다.
또한 본 발명의 조성물 및 방법은 상기 폴리펩티드의 변형체를 포함한다. 본원에서 사용된 폴리펩티드 "변형체"란 보존적 치환 및/또는 변형에 있어서만 언급되는 폴리펩티드와 상이한 것으로서, 그 폴리펩티드의 치료성, 항원성 및/또는 면역원성을 보유한 폴리펩티드이다. 폴리펩티드 변형체는 동정된 폴리펩티드와 약 70% 이상, 더욱 바람직하게는 약 90% 이상, 가장 바람직하게는 95% 이상의 동일성을 나타낸다. 면역 반응성을 가진 폴리펩티드의 경우, 상기 폴리펩티드중 하나의 아미노산 서열을 변형시키고, 변형된 폴리펩티드의 면역 반응성을 평가함으로써 변형체를 동정할 수도 있다. 진단용 결합제의 생성에 유용한 폴리펩티드의 경우에, 변형된 폴리펩티드가 결핵의 유무를 검출하는 항체를 생성시키는 능력을 평가함으로써 변형체를 동정할 수 있다. 한편, 본 발명의 진단 방법에 유용하게 이용할 수 있는 본원에서 청구하는 항원의 변형체는 변형된 폴리펩티드가 결핵에 감염된 환자의 혈청에 존재하는 항체를 검출하는 능력을 평가하여 동정할 수 있다. 이러한 변형 서열은, 예컨대, 본원에 기재하는 대표적인 절차를 사용하여 제조하고 테스트할 수 있다.
"보존적 치환"이란 펩티드 화학 분야의 당업자가 폴리펩티드의 2차 구조 및 수치료성이 실질적으로 변화되지 않는 것으로 예측할 수 있도록, 아미노산을 유사한 성질을 가진 또 다른 아미노산으로 치환하는 것을 말한다. 일반적으로, 다음 아미노산 군이 보존적 변화를 나타낸다: (1) ala, pro, gly, glu, asp, gln, asn, ser, thr; (2) cys, ser, tyr, thr; (3) val, ile, leu, met, ala, phe; (4) lys, arg, his; 및 (5) phe, tyr, trp, his.
변형체는 또한 폴리펩티드의 면역원성, 2차 구조 및 수치료성(hydropathic)에 미치는 영향이 최소인 아미노산의 결실 또는 부가와 같은 방법으로 변형시킬 수 있다. 예컨대, 폴리펩티드는 해독과 동시에 또는 해독 후에 단백질의 전달을 지령하는 단백질의 N-말단의 시그널(또는 리더) 서열에 접합시킬 수 있다. 폴리펩티드는 또한 폴리펩티드의 합성, 정제 또는 동정을 용이하게 하기 위한 링커 또는 기타 서열(예컨대, 폴리-His)에, 또는 폴리펩티드의 고체 지지체에의 결합을 강화시키기 위한 링커 또는 기타 서열에 접합시킬 수 있다. 예컨대, 폴리펩티드는 면역글로불린 Fc 영역에 접합시킬 수 있다.
일반적으로, 엠. 투베르쿨로시스 항원 및 이 항원을 코딩하는 DNA 서열은 다양한 방법 중 임의의 것을 이용하여 제조할 수 있다. 예컨대, 엠. 투베르쿨로시스에서 유래한 게놈 또는 cDNA 라이브러리를 하나 이상의 엠. 투베르쿨로시스 면역 개체로부터 얻은 말초혈 단핵 세포(PBMC)나 T 세포주 또는 T 세포 클론을 사용하여 직접 스크리닝할 수 있다. 직접 라이브러리 스크리닝은 일반적으로 엠. 투베르쿨로시스 면역 개체에서 유래한 T 세포에서 증식 및/또는 인터페론-γ생성을 유도하는 능력에 대해, 발현된 재조합 단백질의 푸울(pool)을 분석하여 수행할 수 있다. 상기한 바와 같이 항체 반응성에 기초하여 잠재 T 세포 항원을 먼저 스크리닝할 수 있다.
한편, 항원들을 코딩하는 DNA 서열을 엠. 투베르쿨로시스에 감염된 환자로부터 얻은 혈청을 사용하여 적절한 엠. 투베르쿨로시스 게놈 또는 cDNA 발현 라이브러리를 스크리닝하여 동정할 수 있다. 그러한 스크리닝은 일반적으로 당업자에게 널리 알려진 기법, 예컨대, 문헌[Sambrook 등, Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratories, Cold Spring Harbor, 뉴욕, 1989]에 기재된 기법을 이용하여 수행할 수 있다.
그 후 정제된 항원을, 예컨대 본원에 개시된 대표적인 방법을 이용하여 적절한 면역 반응(예컨대, 세포성 면역 반응)을 유도하는 능력에 대해 평가한다. 그 다음, 면역원성 항원을 전통적인 에드먼(Edman) 화학과 같은 기법을 사용하여 부분적으로 서열 분석할 수 있다. Edman 및 Berg의 문헌[Eur. J. Biochem. 80:116-132, 1967] 참조. 또한, 면역원성 항원은 이 항원을 코딩하는 DNA 서열을 발현 벡터내로 삽입하고 이를 적절한 숙주에서 발현시킴으로써 재조합에 의해 생산할 수 있다.
본 발명의 항원을 코딩하는 DNA 서열은 또한 분리된 항원의 부분 아미노산 서열에서 유래한 축퇴성 올리고뉴클레오티드에 하이브리드화하는 DNA 서열에 대해 적절한 엠. 투베르쿨로시스 cDNA 또는 게놈 DNA 라이브러리를 스크리닝하여 얻을 수도 있다. 그러한 스크리닝에 사용하는 축퇴성 올리고뉴클레오티드 서열은 문헌[Sambrook 등, Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratories, Cold Spring Harbor, 뉴욕, 1989] 및 여기에 인용된 참조 문헌에 기재된 바와 같이 디자인하고, 합성하여, 스크리닝을 수행할 수 있다. 당해 분야에 널리 알려진 방법으로 상기 올리고뉴클레오티드를 사용하는 폴리머라제 연쇄 반응(PCR)을 이용하여 cDNA 또는 게놈 라이브러리로부터 핵산 프로브를 분리할 수도 있다. 그 후, 분리된 프로브를 사용하여 라이브러리 스크리닝을 수행할 수 있다.
제조 방법과는 무관하게, 본원에 개시된 항원(및 그 면역원성 부분)은 면역 원 반응을 유도하는 능력을 가진다. 보다 구체적으로, 항원은 엠. 투베르쿨로시스 면역 개체에서 유래한 T 세포, NK 세포, B 세포 및/또는 대식세포에서 증식 및/또는 시토킨 생성(즉, 인터페론-γ및/또는 인터루킨-12 생성)을 유도하는 능력을 갖는다. 항원에 대한 면역원성 반응을 평가하는 데 사용하기 위한 세포 유형의 선택은 목적하는 반응에 따라 좌우된다. 예컨대, 인터루킨-12 생성은 B 세포 및/또는 대식세포를 함유하는 제제를 사용하여 평가하는 것이 가장 쉽다. 엠. 투베르쿨로시스 면역 개체는 엠. 투베르쿨로시스에 대한 효과적인 T 세포 반응을 일으킴으로써 결핵의 발병에 저항하는 것으로 간주되는 개체(실질적으로 질병의 증상이 없는 개체)를 말한다. 이러한 개체는 결핵 단백질(PPD)에 대한 피내 피부 테스트 반응이 강한 양성을 보이고(즉, 직경이 약 10 ㎜보다 큰 경결을 나타냄), 결핵의 어떠한 징후나 증상도 없음에 근거하여 식별할 수 있다. 엠. 투베르쿨로시스-면역 개체에서 유래한 T 세포, NK 세포, B 세포 및 대식세포는 당업자에게 알려진 방법을 사용하여 준비할 수 있다. 예컨대, PBMC(즉, 말초혈 단핵 세포)의 제제는 성분 세포의 추가 분리 없이 이용될 수 있다. 일반적으로 PBMC는, 예컨대 피콜(FicollTM)(뉴욕주 윈스롭 래보러토리즈)을 통한 밀도 원심분리를 이용하여 준비할 수 있다.
또한, 본원에 기재된 분석에 사용하기 위한 T 세포는 PBMC로부터 직접 정제할 수도 있다. 한편, 마이코박테리아 단백질에 대해 반응성이 있는 농축된 T 세포주 또는 개체의 마이코박테리아 단백질에 대해 반응성이 있는 T 세포 클론을 이용할 수도 있다. 이러한 T 세포 클론은 예컨대, 엠. 투베르쿨로시스 면역 개체에서 유래한 PBMC를 마이코박테리아 단백질과 함께 2∼4주 동안 배양하여 생성시킬 수 있다. 이 과정은 마이코박테리아 단백질에 특이적인 T 세포만을 증산하여 그러한 세포만으로 구성된 세포주를 생성시킨다. 당업자에게 알려진 방법에 의해 이들 세포를 클로닝하고 개개의 단백질을 사용하여 테스트하여, 개체의 T 세포 특이성을 보다 정확히 확인할 수 있다. 일반적으로, 엠. 투베르쿨로시스 면역 개체에서 유래한 T 세포, NK 세포, B 세포 및/또는 대식세포를 사용하여 수행한 증식 및/또는 시토킨 생성(즉, 인터페론-γ및/또는 인터루킨-12 생성)에 대한 분석에서 테스트에 양성 반응을 보이는 항원은 면역원성이 있는 것으로 간주된다. 이 분석은, 예컨대 후술하는 대표적인 절차를 사용하여 수행할 수 있다. 이러한 항원의 면역원성 부분은 유사한 분석을 이용하여 확인할 수 있고, 본원에 개시된 폴리펩티드내에 존재할 수 있다.
폴리펩티드(예, 면역원성 항원 또는 그 부분 또는 기타 변형체)가 세포 증식을 유도하는 능력은 세포들(예컨대, T 세포 및/또는 NK 세포)을 폴리펩티드와 접촉시키고, 이들 세포의 증식을 측정함으로써 평가한다. 일반적으로, 약 105개 세포를 평가하기에 충분한 폴리펩티드의 양은 약 10 ng/㎖∼약 100 ㎍/㎖, 바람직하게는 약 10 ㎍/㎖이다. 세포와 폴리펩티드의 항온처리는 통상적으로 37℃에서 약 6일 동안 수행한다. 폴리펩티드와의 항온처리 후에, 증식 반응에 대해 세포를 분석하는데, 증식 반응은 당업계에 공지된 방법, 예컨대 방사능 표지된 티미딘 펄스에 세포를 노출시키는 단계 및 세포내 DNA로 병입된 표지를 측정하는 단계를 포함하는 방 법으로 평가할 수 있다. 일반적으로, 증식을 백그라운드(즉, 폴리펩티드 없이 배양한 세포에 대해 관찰된 증식)보다 3배 이상 증가시킨 폴리펩티드는 증식을 유도할 수 있는 것으로 본다.
세포내에서 인터페론-γ 및/또는 인터루킨-12의 생성을 자극하는 폴리펩티드의 능력은, 폴리펩티드와 세포를 접촉시키는 단계, 및 세포가 생성하는 인터페론-γ 또는 인터루킨-12의 양을 측정하는 단계를 수행하여 평가할 수 있다. 일반적으로, 약 105개 세포를 평가하기에 충분한 폴리펩티드의 양은 약 10 ng/㎖∼약 100 ㎍/㎖, 바람직하게는 약 10 ㎍/㎖이다. 폴리펩티드는, 고체 지지체, 예컨대 비이드 또는 미국 특허 제4,897,268호 및 제5,075,109호에 개시된 것과 같은 생분해성 미소구상에 고정시킬 수 있으나, 반드시 그럴 필요는 없다. 세포와 폴리펩티드의 항온 처리는 통상 37℃에서 약 6일 동안 수행한다. 폴리펩티드와의 항온처리 후에, 인터페론-γ 및/또는 인터루킨-12(또는 하나 이상의 이의 서브유닛)에 대해 세포를 분석하는데, 이때 당업계에 공지된 방법, 예컨대 효소 결합 면역흡착법(ELISA) 또는 IL-12 P70 헤테로이량체인 경우 T 세포의 증식을 측정하는 방법과 같은 생물학적 분석 방법으로 평가할 수 있다. 일반적으로, 배양된 상청액(1 ㎖당 104∼105개 T 세포 함유) 1 ㎖당 인터페론-γ 50 pg 이상을 생성하는 폴리펩티드는 인터페론-γ의 생성을 자극하는 것으로 볼 수 있다. 105개 대식세포 또는 B 세포당(또는 3 ×105개 PBMC당) IL-12 P70 서브유닛 10 pg/㎖ 이상, 및/또는 IL-12 P40 서브유닛 100 pg/㎖ 이상의 생성을 자극하는 폴리펩티드는 IL-12의 생성을 자극하는 것으로 볼 수 있다.
일반적으로, 면역원성 항원이란 엠. 투베르쿨로시스 면역 개체 약 25% 이상으로부터 유래된 T 세포, NK 세포, B 세포 및/또는 대식 세포에서 증식 및/또는 시토킨 생성(즉, 인터페론-γ 및/또는 인터루킨-12 생성)을 자극하는 항원이다. 이들 면역원성 항원 중에서, 치료 특성이 우수한 폴리펩티드는 상기 분석에서 반응 정도와 반응이 관찰된 개체의 비율을 기초로 구별해 낼 수 있다. 또한, 치료 특성이 우수한 항원은 엠. 투베르쿨로시스 면역이 없는 개체의 약 25% 이상에서 유래된 세포에서 시험관내 증식 및/또는 시토킨 생성을 자극하지 않으며, 따라서 특별히 엠. 투베르쿨로시스 반응성 세포에 기인하지 않는 반응을 제거한다. 엠. 투베르쿨로시스 면역 개체에서 유래한 T 세포, NK 세포, B 세포 및/또는 대식 세포 제제의 고비율에서 반응을 유도하는 항원(다른 개체로부터의 세포 제조물 중에서의 반응 빈도는 낮음)은 치료 특성이 우수하다.
치료 특성이 우수한 항원은 백신으로 투여할 때 실험 동물에서 엠. 투베르쿨로시스 감염의 심각도를 감소시키는 능력을 기초로 하여 동정할 수 있다. 실험 동물에 사용하기에 적합한 백신 제제는 하기에 상세히 설명되어 있다. 효능은 실험 감염 후에 박테리아 수를 약 50% 이상 감소시키고/시키거나, 사망율을 약 40% 이상 감소시키는 항원의 능력을 근거로 하여 결정할 수 있다. 적절한 실험 동물로는 마우스, 기니아 피그 및 영장류가 있다.
일반적으로 진단 특성이 우수한 항원은, 활성 투베르쿨로시스가 있는 개체에 서 수행되는 피내 피부 테스트에서 반응을 유발할 수 있지만, 엠. 투베르쿨로시스에 감염되지 않은 개체에서 수행되는 테스트에서는 반응을 유발할 수 없는 능력을 기초로 하여 동정할 수 있다. 피부 테스트는 일반적으로 후술하는 바와 같이 수행할 수 있으며, 5 mm 이상의 경결 반응을 나타내면 양성인 것으로 간주한다.
본원에 개시된 항원의 면역원성 부분은 공지된 기법, 예컨대 Paul의 문헌[Fundamental Immunology, 3d ed., Raven Press, 1993, p243-247] 및 본원의 참고 인용문에 요약된 바와 같은 기법을 사용하여 제조 및 동정할 수 있다. 이러한 기법은 면역원성이 있는 천연 항원의 폴리펩티드 부분을 스크리닝하는 단계를 포함한다. 본원에 개시된 대표적인 증식 및 시토킨 생성 분석법은 대체로 상기 스크리닝에 사용될 수 있다. 폴리펩티드의 면역원성 부분은, 대표적인 분석법내에서 전길이 항원이 생성하는 것과 거의 유사한 면역 반응(예, 증식, 인터페론-γ 생성 및/또는 인터루킨-12 생성)을 유발하는 부분이다. 즉, 항원의 면역원성 부분은 본원에 개시된 모델 증식 분석법에서 전길이 항원이 유도하는 증식의 약 20% 이상, 바람직하게는 약 100%를 유도할 수 있다. 또한 면역원성 부분은 본원에 개시된 모델 분석에서 전길이 항원이 유도하는 인터페론-γ 및/또는 인터루킨-12의 약 20% 이상, 바람직하게는 약 100%의 생성을 자극할 수 있다.
엠. 투베르쿨로시스 항원의 부분 및 기타 변형체는 합성 또는 재조합 수단으로 제조할 수 있다. 약 100개 아미노산 미만, 일반적으로 약 50개 아미노산 미만의 합성 폴리펩티드는 당업계에 공지된 기법을 이용하여 제조할 수 있다. 예를 들어, 이러한 폴리펩티드는 상업적으로 이용되는 고상 기법, 예컨대 Merrifield 고상 합 성법을 이용하여 합성할 수 있으며, 이 방법에서는 아미노산이 성장하는 아미노산 쇄에 순차적으로 부가된다. Merrifield의 문헌[J.Am.Chem.Soc. 85:2149-2146, 1963] 참조. 폴리펩티드의 자동 합성을 위한 장치는 미국 캘리포니아주 포스터 시티의 퍼킨 엘머/어플라이드 바이오시스템즈 디비젼과 같은 공급업체로부터 시판되며, 제조업자의 지시에 따라 작동시킬 수 있다. 천연 항원의 변형체는, 표준 돌연변이 유발 기법, 예컨대 올리고뉴클레오티드에서 유도된 부위 특이적 돌연변이 유발법을 이용하여 제조할 수 있다. 표준 기법을 사용하여 DNA 서열의 일부를 제거하여 절두된 폴리펩티드를 제조할 수도 있다.
천연 항원의 부분 및/또는 변형체를 포함하는 재조합 폴리펩티드는 당업계에 공지된 각종 기법을 이용하여 폴리펩티드를 코딩하는 DNA 서열로부터 쉽게 제조할 수 있다. 예를 들어, 재조합 단백질을 배양 배지내로 분비하는 적절한 숙주/벡터계에서 얻은 상청액을 먼저 시판용 필터를 사용하여 농축시킬 수 있다. 농축 후에, 농축물을 친화도 매트릭스 또는 이온 교환 수지와 같은 적절한 정제 매트릭스에 적용할 수 있다. 마지막으로, 하나 이상의 역상 HPLC 단계를 사용하여 재조합 단백질을 추가로 정제할 수 있다.
당업계에 공지된 임의의 각종 발현 벡터를 사용하여 본 발명의 재조합 폴리펩티드를 발현시킬 수 있다. 재조합 폴리펩티드를 코딩하는 DNA 분자를 포함하는 발현 벡터로 형질전환 또는 형질감염시킨 임의의 적절한 숙주 세포에서 발현시킬 수 있다. 적절한 숙주 세포로는 원핵세포, 효모 및 고등 진핵세포가 있다. 사용된 숙주 세포는 이. 콜라이, 효모 또는 포유류 세포, 예컨대 COS 또는 CHO가 바람직하 다. 이러한 방식으로 발현된 DNA 서열은 자연 발생적인 항원, 자연 발생적인 항원의 부분 또는 이의 변형체를 코딩할 수 있다.
일반적으로, 본원에 개시된 폴리펩티드는 제조 방법과 관계없이 실질적으로 순수한 형태로 제조된다. 폴리펩티드는 바람직하게는 약 80% 이상, 더욱 바람직하게는 약 90% 이상, 가장 바람직하게는 약 99% 이상의 순도를 갖는다. 특정 바람직한 구체예에서, 하기에 상세히 설명된 바와 같이, 본원에 개시된 하나 이상의 방법에 사용하기 위한 약학 조성물 또는 백신내로 실질적으로 순수한 폴리펩티드를 병입시킨다.
한 구체예에서, 본 발명은 (a) 서열 번호 1-12, 83, 102-108, 125, 127-137, 139 및 140의 DNA 서열; (b) 이 DNA 서열의 상보 서열, 또는 (c) (a) 또는 (b)의 서열에 실질적으로 상동성인 DNA 서열에 의해 코딩되는 1종 이상의 아미노산 서열을 포함하는 엠. 투베르쿨로시스 항원(또는 이러한 항원의 변형체)의 면역원성 부분을 하나 이상 포함하는 폴리펩티드를 개시하고 있다. 관련 구체예에서, 본 발명은 서열 번호 16-33, 109, 126, 138, 141, 142에 제공된 서열 및 이의 변형체로 구성된 군에서 선택되는 아미노산 서열을 가진 엠. 투베르쿨로시스 항원의 면역원성 부분을 하나 이상 포함하는 폴리펩티드를 제공한다.
본원에서 제공된 엠. 투베르쿨로시스 항원은 본원에 구체적으로 기술된 1종 이상의 DNA 서열에 실질적으로 상동성인 DNA 서열에 의해 코딩되는 변형체를 포함한다. 본원에서 사용한 "실질적인 상동성"은 보통의 엄중 조건하에 하이브리드화할 수 있는 DNA 서열을 의미한다. 적절한 보통의 엄중 조건은 5 ×SSC, 0.5% SDS, 1.0 mM EDTA(pH 8.0) 용액에서의 예비 세척; 50∼65℃, 5 ×SSC에서 밤새, 또는 종간 상동성의 경우 45℃, 0.5 ×SSC에서 하이브리드화; 및 0.1% SDS를 함유하는 2 ×SSC, 0.5 ×SSC 및 0.2 ×SSC를 각각 사용한 65℃에서의 20분간의 2회 세척을 포함한다. 이러한 하이브리드화 DNA 서열은 본 발명의 범위에 속하며, 코드 축퇴성으로 인해 하이브리드화 DNA 서열에 의해 코딩되는 면역원성 폴리펩티드를 코딩하는 뉴클레오티드 역시 본 발명에 속한다.
관련 양태에서, 본 발명은 본 발명의 제1 폴리펩티드 및 제2 폴리펩티드를 포함하는 융합 단백질, 또는 대안적으로 본 발명의 폴리펩티드 및 공지된 엠. 투베르쿨로시스 항원, 예컨대 Andersen 및 Hansen 등의 문헌[Infect. Immun. 57:2481-2488, 1989 (젠뱅크 수탁 번호 M30046)]에 개시된 38 kD 항원, 또는 엠. 보비스(수탁 번호 U34848) 및 엠. 투베르쿨로시스(Sorensen 등, Infec. Immun. 63:1710-1717, 1995)에서 이전에 동정된 ESAT-6을 포함하는 융합 단백질을 제공한다. 이러한 융합 단백질의 변형체도 제공된다. 본 발명의 융합 단백질은 제1 폴리펩티드 및 제2 폴리펩티드 사이에 링커 펩티드를 포함할 수 있다.
본 발명의 융합 단백질을 코딩하는 DNA 서열은 공지된 재조합 DNA 기법을 사용하여 작제하여 제1 폴리펩티드 및 제2 폴리펩티드를 코딩하는 별개의 DNA 서열을 적절한 발현 벡터내로 회합시킨다. 제1 폴리펩티드를 코딩하는 DNA 서열의 3' 말단을, 펩티드 링커를 사용하거나, 또는 사용하지 않고, 제2 폴리펩티드를 코딩하는 DNA 서열의 5' 말단에 결찰시켜, 서열의 리딩 프레임이 2개의 DNA 서열의 mRNA가 제1 폴리펩티드 및 제2 폴리펩티드 둘다의 생물학적 활성을 보유하는 단일 융합 단 백질로 해독되도록 하는 상태가 되게 한다.
펩티드 링커 서열을 사용하여 각 폴리펩티드를 2차 구조 및 3차 구조로 폴딩시키기에 충분한 거리로 제1 폴리펩티드 및 제2 폴리펩티드를 분리시킬 수 있다. 이러한 펩티드 링커 서열은 당업계에 공지된 표준 기법을 사용하여 융합 단백질내로 병입시킨다. 적절한 펩티드 링커 서열은 다음과 같은 인자를 기초로 선택할 수 있다. (1) 가요성이 있는 연장된 구조를 형성할 수 있는 능력; (2) 제1 폴리펩티드 및 제2 폴리펩티드상의 기능성 에피토프와 상호작용할 수 있는 2차 구조를 형성할 수 있는 능력의 부재; (3) 폴리펩티드 기능성 에피토프와 반응할 수 있는 소수성 잔기 또는 하전된 잔기의 결핍. 바람직한 펩티드 링커 서열의 예로는 Gly, Asn 및 Ser 잔기가 있다. 기타 중성에 가까운 천연 아미노산, 예컨대 Thr 및 Ala 역시 링커 서열에 사용할 수 있다. 링커로서 유용하게 사용될 수 있는 아미노산 서열은 Maratea 등의 문헌[Gene 40:39-46, 1985; Murphy 등, Proc.Natl.Acad.Sci. USA 83:8258-8262, 1986], 미국 특허 제4,935,233호 및 미국 특허 제4,751,180호에 개시된 아미노산 서열을 포함한다. 링커 서열은 길이가 1개∼약 50개인 아미노산일 수 있다. 제1 폴리펩티드 및 제2 폴리펩티드가 기능성 도메인을 분리하고 입체 방해를 방지하는 데 사용될 수 있는 비필수 N 말단 아미노산 영역을 보유하는 경우, 펩티드 서열은 필요하지 않다.
결찰된 DNA 서열은 적절한 전사 또는 해독 조절 성분에 작동가능하게 결합된다. DNA 발현을 담당하는 조절 성분은 제1 폴리펩티드를 코딩하는 DNA 서열의 5'에만 위치한다. 유사하게, 종지 코돈은 제2 폴리펩티드를 코딩하는 DNA 서열의 3'에 만 존재한다.
또 다른 양태에서, 본 발명은 1종 이상의 상기 폴리펩티드 또는 융합 단백질(또는 이러한 폴리펩티드를 코딩하는 DNA 분자)를 사용하여 환자에서 결핵에 대한 예방 면역성을 유도하는 방법을 제공한다. 본원에서 "환자"는 임의의 온혈 동물, 바람직하게는 인간을 의미한다. 환자는 질병에 걸린 사람일 수도 있고, 또는 검출가능한 질병 및/또는 감염이 없는 사람일 수도 있다. 즉, 예방 면역성은 결핵을 예방하거나 치료하기 위해 유도할 수 있다.
이러한 양태에서, 폴리펩티드, 융합 단백질 또는 DNA 분자는 일반적으로 약학 조성물 및/또는 백신내에 존재한다. 약학 조성물은 1종 이상의 폴리펩티드를 포함할 수 있으며, 각 폴리펩티드는 1종 이상의 상기 서열(또는 이의 변형체)와 생리적 허용 담체를 포함할 수 있다. 백신은 1종 이상의 상기 폴리펩티드 및 비특이적 면역 반응 인핸서, 예컨대 면역 증강제(adjuvant) 또는 리포좀(그 내부에 폴리펩티드가 병입되어 있음)을 포함할 수 있다. 이러한 약학 조성물 및 백신은 기타 엠. 투베르쿨로시스 항원을, 조합 폴리펩티드내로 병입시키거나 또는 별도의 폴리펩티드내에 존재하도록 하여 포함할 수도 있다.
대안적으로, 백신은 폴리펩티드가 동일계에서 생성될 수 있도록 전술한 1종 이상의 폴리펩티드를 코딩하는 DNA를 포함할 수 있다. 이러한 백신에서, DNA는 핵산 발현계, 박테리아 발현계 및 바이러스 발현계를 비롯하여 당업계에 공지된 임의의 각종 전달계내에 존재할 수 있다. 적절한 핵산 발현계는 환자내에서의 발현을 위해 필수적인 DNA 서열(예, 적절한 프로모터 및 종결 시그널)을 포함한다. 박테리 아 전달계는 세포 표면상에 폴리펩티드의 면역원성 부분을 발현하는 박테리아(예, 바실러스-칼메트-구에린)을 투여하는 것을 포함한다. 바람직한 구체예에서, DNA는 바이러스 발현계(예, 백시니아 또는 기타 폭스 바이러스, 레트로바이러스 또는 아데노바이러스)를 사용하여 도입할 수 있으며, 바이러스 발현계는 비병원성(불완전), 복제 컴피턴트 바이러스의 사용을 포함할 수 있다. 이러한 발현계로 DNA를 병입시키기 위한 기술은 당업계에 공지되어 있다. DNA는, 예컨대 Ulmer 등의 문헌[Science 259:1745-1749, 1993]에 개시되어 있고, Cohen의 문헌[Science 259:1691-1692, 1993]에 검토된 바와 같이 "나출(裸出; naked)상태"일 수 있다. 나출 상태의 DNA 흡수율은 세포 내로 효과적으로 이송되는 생분해성 비이드상에 DNA를 코팅하여 증가시킬 수 있다.
관련 양태에서, 전술한 DNA 백신은 본 발명의 폴리펩티드 또는 공지된 엠. 투베르쿨로시스 항원, 예컨대 전술한 38 kD 항원과 동시에 또는 순차적으로 투여할 수 있다. 예를 들어, 전술한 바와 같이 "나출 상태로" 또는 전달계를 이용하여 본 발명의 폴리펩티드를 코딩하는 DNA를 투여한 다음 항원을 투여하여 백신의 예방 면역 효과를 증강시킬 수 있다.
투여 경로 및 빈도뿐 아니라 용량을 개체별로 다양하게 하여, 현재 BCG를 사용한 면역화에 이용되고 있는 것과 동일하게 사용할 수 있다. 일반적으로 약학 조성물 및 백신은 주사(예, 피내, 근육내, 정맥내 또는 피하), 비강내(예, 흡출) 또는 경구로 투여할 수 있다. 1∼36 주간 동안 1∼3회 용량을 투여할 수 있다. 3∼4 개월의 간격으로 3회 용량을 투여하고, 그 후 추가 백신 접종을 주기적으로 한다. 환자 개개인마다 다른 프로토콜이 적절할 수 있다. 적절한 용량은 전술한 바와 같이 투여했을 때 1∼2년 동안 면역화된 환자내에서 엠. 투베르쿨로시스 감염으로부터 환자를 보호하기에 충분한 면역 반응을 유발시킬 수 있는 폴리펩티드 또는 DNA의 양이다. 일반적으로, 1회 용량내에 존재하는 (또는 1회 용량내의 DNA에 의해 숙주 내에서 생성되는) 폴리펩티드의 양은 숙주 1 kg당 약 1 pg∼약 100 ㎎, 통상적으로 약 10 pg∼약 1 ㎎, 바람직하게는 약 100 pg∼약 1 ㎍일 수 있다. 적절한 용량 크기는 환자의 체격에 따라 다양할 수 있지만, 통상 약 0.1 ㎖∼약 5 ㎖이다.
당업자에게 공지된 임의의 적절한 담체가 본 발명의 약학 조성물에 사용될 수 있지만, 담체의 유형은 투여 방식에 따라 달라진다. 피하 주사와 같은 비경구 투여의 경우, 담체는 물, 염수, 알코올, 지질, 왁스 또는 완충액을 포함하는 것이 바람직하다. 경구 투여의 경우, 임의의 전술한 담체 또는 고형 담체, 예컨대 만니톨, 락토스, 전분, 스테아르산마그네슘, 나트륨 사카린, 활석, 셀룰로스, 글루코스, 슈크로스 및 탄산마그네슘을 사용할 수 있다. 생분해성 미소구(예, 폴리락틱 갈락티드) 역시 본 발명의 약학 조성물에 대한 담체로서 사용할 수 있다. 적절한 생분해성 미소구는, 미국 특허 제4,897,268호 및 제5,075,109호에 개시되어 있다.
임의의 각종 면역 증강제를 본 발명의 백신에 사용하여 면역 반응을 비특이적으로 증강시킬 수 있다. 대부분의 면역 증강제는 급속한 이화작용으로부터 항원을 보호하도록 고안된 물질, 예컨대 수산화나트륨 또는 광유, 및 면역 반응의 비특이적 자극제, 예컨대 지질 A, 보르타델라 퍼투시스(Bortadella pertussis) 또는 마이코박테리움 투베르쿨로시스(Mycobacterium tuberculosis)를 포함한다. 적절한 면 역 증강제는, 예컨대 프로인트 불완전 보조제 및 프로인트 완전 보조제(디프코 래보러터리즈)와 머크 보조제 65(미국 뉴저지주 라웨이 머크 앤드 캄파니 인코포레이티드) 같이 시판되고 있다. 기타 적절한 면역 증강제로는 명반, 생분해성 미소구, 모노포스포릴 지질 A 및 퀼(quill) A가 있다.
또 다른 양태에서, 본 발명은 피부 테스트를 이용하여 결핵을 진단하는 데 전술한 1종 이상의 폴리펩티드를 사용하는 방법을 제공한다. 본원에서 사용한 "피부 테스트"는, 전술한 1종 이상의 폴리펩티드의 피내 주사후에 지연형 과민(DTH) 반응(예, 팽윤, 적화(赤化), 피부염)을 측정하여 환자에서 직접 수행되는 임의의 분석법이다. 이러한 주사는 환자의 피부 세포와 폴리펩티드(들)를 접촉시키기에 충분한 임의의 장치, 예컨대 투베르쿨린 주사기 또는 1 ㎖ 주사기를 사용하여 수행할 수 있다. 반응은 바람직하게는 주사 후 48 시간 이상, 더욱 바람직하게는 주사 후 48∼72 시간 후에 측정한다.
DTH 반응은 세포 매개 면역 반응으로서, 이 반응은 미리 테스트 항원(즉, 사용된 폴리펩티드의 면역원성 부분 또는 이의 변형체)에 노출된 환자에게서 보다 크게 나타난다. 반응은 룰러(ruler)를 사용하여 시각적으로 측정할 수 있다. 일반적으로 직경이 약 0.5 cm 이상, 바람직하게는 약 1.0 cm 이상인 반응은 결핵 감염임을 나타내는 양성 반응이며, 이 경우 활성 질병으로 나타날 수도 나타나지 않을 수도 있다.
본 발명의 폴리펩티드는 전술한 바와 같은 폴리펩티드 및 생리적 허용 담체를 포함하는 약학 조성물로서 피부 테스트에 사용하기 위해 제형화하는 것이 바람 직하다. 이러한 조성물은 통상적으로 1종 이상의 상기 폴리펩티드를 0.1 ㎖의 부피내에 약 1 ㎍∼약 100 ㎍, 바람직하게는 약 10∼50 ㎍ 양으로 포함할 수 있다. 이러한 약학 조성물내에 사용된 담체는 페놀 및/또는 트윈 80TM 과 같은 적절한 보존제가 함유된 염수 용액이다.
바람직한 구체예에서, 피부 테스트에 사용되는 폴리펩티드는 반응 기간 동안 주사 부위에 남아 있기에 충분한 크기이다. 일반적으로, 아미노산 길이가 9개 이상 인 폴리펩티드면 충분하다. 또한, 폴리펩티드는 주사한지 수시간내에 대식세포에 의해 분해되어 T 세포에 제시되는 것이 바람직하다. 이러한 폴리펩티드는 상기 1종 이상의 서열 및/또는 기타 면역원성 또는 비면역원성 서열의 반복체를 포함할 수 있다.
다음 실시예는 예시를 위해 제공되는 것이며, 본 발명을 제한하려는 것은 아니다.
실시예
실시예 1
인간 PBMC에서 얻은 CD4+ T 세포주를 이용한 엠. 투베르쿨로시스 폴리펩티드의 정제 및 특성 규명
본 발명의 엠. 투베르쿨로시스 항원은 실질적으로 문헌[Sanderson et al. J.Exp.Med., 1995, 182:1751-1757]에 기재된 바와 같이 엠. 투베르쿨로시스 균주 H37Rv 및 Erdman의 cDNA 라이브러리를 발현 클로닝하여 분리하였고, 이것은 면역반 응성 T 세포주내에서 IFN-γ및 PBMC 증식을 유도하는 것으로 확인되었다.
수상돌기 세포를 엠. 투베르쿨로시스로 감염시켜 DC-4 및 DC-5라고 칭하는 2가지 CD4+ T 세포주를 만들었다. 구체적으로, 단일 공여체에서 얻은 유착성 PBMC로부터 수상돌기 세포를 얻은 뒤 투베르쿨로시스로 감염시켰다. 동일 공여체 유래의 림프구를 한계 희석 조건하에 감염된 수상돌기 세포와 함께 배양하여 CD4+ T 세포주 DC-4 및 DC-5를 만들었다. 이 세포주는 Tb38-1이 아닌 엠. 투베르쿨로시스 유래의 미정제 가용성 단백질과 반응하는 것으로 나타났다. 다시, 한계 희석 조건을 사용하여 DC-6이라 칭한 제3의 CD4+ T 세포주를 얻었으며, 이 세포주는 미정제 가용성 단백질 및 Tb38-1과 모두 반응하는 것으로 나타났다.
엠. 투베르쿨로시스 균주 H37Rv 및 Erdman으로부터 게놈 DNA를 분리하고, 이것과 람다 ZAP 발현계(미국 캘리포니아주 라졸라에 소재하는 스트라타진 제품)를 사용하여 벡터 pBSK(-)로 발현 라이브러리를 작제하였다. 이 라이브러리를 이. 콜라이로 형질전환시키고, 유도된 이. 콜라이 배양물의 푸울을 수상돌기 세포와 항온배양한 뒤, 그 결과 얻어지는 항온배양된 수상돌기 세포가 CD4+ T 세포주 DC-6의 세포 증식과 IFN-γ생성을 자극하는 능력을 하기 실시예 2에 기재된 바와 같이 관찰하였다. 양성의 푸울을 분획하여, 순수 엠. 투베르쿨로시스 클론이 얻어질 때까지 재테스트하였다. 19개의 클론을 분리하였고, 이중 9개는 미국 특허 출원 08/533,634에 개시된 종래 동정된 엠. 투베르쿨로시스 항원 TbH-9 및 Tb38-1을 포함하는 것으로 확인되었다. 나머지 10개의 클론(이하, Tb224, Tb636, Tb424, Tb436, Tb398, Tb508, Tb441, Tb475, Tb488 및 Tb465)의 cDNA 서열을 분석하여 각 각 서열 1∼10에 기재하였다. 이에 대응하는 Tb224 및 Tb636의 추론 아미노산 서열은 각각 서열 13과 14에 기재하였다. 이들 두 항원의 오픈 리딩 프레임은 TbH-9와 상동성이 약간 있는 것으로 확인되었다. 또한, Tb224와 Tb636은 중첩 클론인 것으로 확인되었다.
또, Tb424, Tb436, Tb398, Tb508, Tb441, Tb475, Tb488 및 Tb465는 각각 2개의 작은 오픈 리딩 프레임(ORF-1 및 ORF-2라 칭함) 또는 이것의 절두형을 포함하는 것으로 확인되었으며, 이와 함께 각 클론에 대해 ORF-1 및 ORF-2에 약간의 변형이 있는 것도 확인되었다. Tb424, Tb436, Tb398, Tb508, Tb441, Tb475, Tb488 및 Tb465의 ORF-1 및 ORF-2에 해당하는 추론 아미노산 서열은 서열 16과 17, 18과 19, 20과 21, 22와 23, 24와 25, 26과 27, 28과 29 및 30과 31에 각각 제시하였다. 또한, 클론 Tb424와 Tb436은 ORF-U라고 칭하는 분명한 제3의 오픈 리딩 프레임을 포함하는 것으로 확인되었다. Tb424 및 Tb436의 ORF-U에 대한 추론 아미노산 서열은 각각 서열 32 및 33에 기재하였다. Tb424 및 Tb436은 중첩 클론 또는 유사 중복/트란스포즈 카피인 것으로 확인되었다. 이와 유사하게, Tb398, Tb508 및 Tb465도 Tb475 및 Tb488과 마찬가지로 중첩 클론 또는 유사 중복/트란스포즈 카피인 것으로 확인되었다.
이 서열들을 BLASTN 시스템을 사용하여 젠뱅크의 공지 서열과 비교하였다. 항원 Tb224 및 Tb431과 상동성이 있는 서열은 찾을 수 없었다. Tb636은 종래 엠. 투베르쿨로시스에서 동정된 코스미드와 100% 동일한 것으로 확인되었다. 이와 유사하게 Tb508, Tb488, Tb398, Tb424, Tb436, Tb441, Tb465 및 Tb475도 공지의 엠. 투 베르쿨로시스 코스미드와 상동성이 있는 것으로 확인되었다. 또한, Tb488은 엠. 투베르쿨로시스 토포이소머라제 I과 100% 상동성이 있는 것으로 확인되었다.
오픈 리딩 프레임 ORF-1에 대한 17가지 중첩 펩티드(각각 1-1∼1-17이라 칭함, 서열 34∼50)와 오픈 리딩 프레임 ORF-2에 대한 30가지 중첩 펩티드(이하, 2-1∼2-30이라 칭함, 서열 51∼80)를 이하 실시예 3에 기재된 절차에 따라 합성하였다.
합성 펩티드, 재조합 ORF-1 및 ORF-2가 PPD 양성 공여체 유래의 PBMC에서 IFN-γ생성과 T 세포 증식을 유도하는 능력은 하기 실시예 2에 기재된 바와 같이 분석하였다. 도 1a와 1b 및 2a와 2b는 각각 D7 및 D160이라 칭한 2가지 공여체의 재조합 ORF-2 및 합성 펩티드 2-1∼2-16에 의한 T 세포 증식 및 IFN-γ의 자극에 대하여 예시한 것이다. 재조합 ORF-2(이하 MTI라고 칭함)는 2가지 공여체 모두의 PBMC에서 T 세포 증식과 IFN-γ생성을 자극하였다. 각 합성 펩티드에 의해 관찰되는 PBMC 자극의 양은 각 공여체마다 달랐는데, 이것은 각 공여체가 ORF-2상의 여러 에피토프를 인식한다는 것을 시사하는 것이다. ORF-1, ORF-2 및 ORF-U가 코딩하는 단백질은 각각 MTS, MTI 및 MSF라고 명명하였다.
MSF의 서열에 대한 18가지 중첩 펩티드(각각 MSF-1∼MSF-18, 서열 번호 84∼101)를 합성하고, 엠. 투베르쿨로시스 배양 여과물에 대하여 생성된 CD4+ T 세포주내 T 세포 증식 및 IFN-γ 생성을 자극하는 각각의 능력을 이하 기재된 바와 같이 조사하였다. MSF-12 및 MSF-13이라 칭한 펩티드(각각, 서열 95 및 96)가 가장 높은 반응도를 나타내는 것으로 확인되었다. 또한, Tb224의 오픈 리딩 프레임에 대한 2 가지 중첩 펩티드(서열 81 및 82)를 합성하였으며, 이는 PPD 양성 공여체 유래의 PBMC에서 T 세포 증식과 IFN-γ생성을 유도하는 것으로 확인되었다.
전술한 방법에 따라 엠. 투베르쿨로시스에 감염된 수상돌기 세포에 대하여 다른 공여체 유래의 2가지 CD4+ T 세포주를 생성하였다. 이 세포주를 사용하여 전술한 엠. 투베르쿨로시스 cDNA 발현 라이브러리를 스크리닝한 결과, Tb867 및 Tb391이라 칭한 2개의 클론을 분리하였다. 서열 분석된 Tb867의 cDNA 서열은 종래 분리된 엠. 투베르쿨로시스 코스미드 SCY22G10과 동일한 것으로 확인되었고, 후보 반응성 오픈 리딩 프레임은 750 아미노산 엠. 투베르쿨로시스 단백질 키나제를 코딩하였다. Tb391의 서열 분석된 cDNA 서열을 젠뱅크의 서열과 비교한 결과 공지 서열과 유의적인 상동성을 나타내지 않았다.
또 다른 연구로서, 실질적으로 전술한 바와 같이 엠. 투베르쿨로시스 배양 여과물에 대하여 CD4+ T 세포주를 생성하고, 이것을 사용하여 전술한 엠. 투베르쿨로시스 Erdman cDNA 발현 라이브러리를 스크리닝하였다. Tb431, Tb472, Tb470, Tb838 및 Tb962라 칭한 5개의 반응성 클론을 분리하였다. Tb431, Tb472, Tb470 및 Tb838의 서열 분석된 cDNA 서열은 각각 서열 11, 12, 104 및 105에 기재하였고, Tb962의 서열 분석된 cDNA 서열은 서열 106 및 107에 기재하였다. Tb431에 대응하는 추론 아미노산 서열은 서열 15에 제시하였다.
이어서, Tb472의 전길이 cDNA 서열(서열 108)을 분리하는 실험을 실시하였다. 중첩 펩티드를 합성하고, 이를 사용하여 반응성 오픈 리딩 프레임을 확인하였다. Tb472에 의해 코딩된 단백질(MSL이라 칭함)의 추론 아미노산 서열은 서열 109 에 기재하였다. Tb472 및 MSL의 서열을 전술한 바와 같이 젠뱅크의 서열과 비교한 결과 공지 서열과는 상동성을 나타내지 않는 것으로 확인되었다. MSL 서열에 대한 15가지 중첩 펩티드(이하, 각각 MSL-1∼MSL-15라고 칭함; 서열 110∼124)를 합성하고, 엠. 투베르쿨로시스 배양 여과물에 대하여 생성된 CD4+ T 세포주에서 T 세포 증식과 IFN-γ 생성을 자극하는 능력을 이하 기재되는 바와 같이 조사하였다. MSL-10(서열 119) 및 MSL-11(서열 120)이라 칭한 펩티드가 가장 높은 반응성을 나타내는 것으로 확인되었다.
서열 분석된 Tb838의 cDNA 서열을 젠뱅크 중의 서열과 비교한 결과 종래 분리된 엠. 투베르쿨로시스 코스미드 SCY07H7과 동일한 것으로 확인되었다. 클론 Tb962의 서열 분석된 cDNA 서열과 젠뱅크의 서열을 비교한 결과, 1개가 박토페리틴의 일부를 코딩하는 것인 2개의 종래 동정된 엠. 투베르쿨로시스 코스미드와 약간의 상동성을 나타내는 것으로 확인되었다. 하지만, 재조합 박토페리틴은 Tb962를 분리하는 데 사용된 T 세포주와 반응성이 없는 것으로 확인되었다.
전술한 클론 Tb470을 사용하여 TbH9과 상동성을 나타내고 Mtb40이라 칭한 40 kDa 항원을 코딩하는 것으로 밝혀진 전길이 오픈 리딩 프레임(서열 125)을 회수하였다. 서열 분석된 Mtb40의 아미노산 서열은 서열 126에 기재하였다. 이와 유사하게, 이어서 서열 83에 기재된 Tb431의 전길이 cDNA 서열을 분리하였으며, 이는 Mtb40을 코딩하는 오픈 리딩 프레임을 포함하는 것으로 확인되었다. 또한, Tb470과 Tb431은 U-ORF 유사 항원을 코딩하는 잠재적 오픈 리딩 프레임을 포함하는 것으로 확인되었다.
엠. 투베르쿨로시스 배양 여과물에 대하여 생성된 복수의 CD4+ T 세포주로 엠. 투베르쿨로시스 Erdman cDNA 발현 라이브러리를 스크리닝하여 Tb366, Tb433 및 Tb439라고 칭한 3개의 클론을 분리하였다. 서열 분석된 Tb366, Tb433 및 Tb439의 cDNA 서열을 각각 서열 127, 128 및 129에 기재하였다. 이 서열을 젠뱅크의 서열과 비교한 결과 Tb366과 유의적 상동성이 없는 것으로 나타났+다. Tb433은 종래 동정된 엠. 투베르쿨로시스 항원 MPT83과 약간의 상동성이 있는 것으로 확인되었다. Tb439는 종래 동정된 엠. 투베르쿨로시스 코스미드 SCY02B10과 100% 동일성이 있는 것으로 확인되었다.
실질적으로 전술한 바와 같이 엠. 투베르쿨로시스 PPD에 대하여 CD4+ T 세포주를 생성하고, 이것을 사용하여 상기 엠. 투베르쿨로시스 Erdman cDNA 발현 라이브러리를 스크리닝하였다. 1개의 반응성 클론(Tb372라고 칭함)을 분리하고, 서열 분석된 cDNA 서열을 서열 번호 130 및 131에 기재하였다. 이 서열을 젠뱅크의 서열과 비교한 결과 유의적 상동성이 있는 서열은 발견되지 않았다.
이어서, 전술한 바와 같이 투베르쿨로시스로 8일간 감염시킨 수상돌기 세포에 대하여 생성된 CD4+ T 세포주로 엠. 투베르쿨로시스 cDNA 발현 라이브러리를 스크리닝하여 Tb390R5C6 및 Tb390R2C11로 칭한 2개의 클론을 분리하였다. 서열 분석된 Tb390R5C6의 cDNA 서열은 서열 132에 기재하고, Tb390R2C11의 cDNA 서열은 서열 133 및 134에 기재하였다. Tb390R5C6은 종래 동정된 엠. 투베르쿨로시스 코스미드와 100% 동일성이 있는 것으로 확인되었다.
그 다음, 전술한 방법을 사용하여 제조된 엠. 투베르쿨로시스 게놈 DNA 라이 브러리를 다음과 같이 스크리닝하였다. 엠. 투베르쿨로시스 Erdman 균주의 게놈 DNA를 평균 2 kb의 크기로 무작위 절단하고 클리나우 폴리머라제로 평활 말단화한 뒤, EcoRI 어댑터를 부가하였다. 이 삽입체를 스크린 파지 벡터(미국 위스콘신주 매디슨에 소재하는 노바젠 제품)에 결찰시키고 파지메이커 추출물(노바젠 제품)을 사용하여 시험관내에서 팩키징하였다. 이 파지 라이브러리(Erd λ스크린 라이브러리라 칭함)를 증폭시키고 그 일부를 자가서브클로닝 기작으로 이. 콜라이 균주 BM25.8(노바젠)을 사용하여 플라스미드 발현 라이브러리로 전환시켰다. pSCREEN 재조합체를 함유하는 BM25.8 배양물로부터 플라스미드 DNA를 정제하고 이것을 사용하여 발현 숙주 균주 BL21(DE3)pLysS의 컴피턴트 세포를 형질전환시켰다. 형질전환된 세포를 96웰 미량역가 평판에 각 웰당 약 50개의 콜로니를 보유하도록 분액하였다. 96웰 플라스미드 라이브러리 포맷의 레플리카 평판을 재조합 단백질을 발현하도록 IPTG로 유도하였다. 유도 후, 평판을 원심분리하여 이. 콜라이를 침전시키고, 이것을 전술한 바와 같이 PPD 양성 공여체(공여체 160)로 만든 CD4+ T 세포주의 T 세포 발현 클로닝에 직접 사용하였다. 엠. 투베르쿨로시스 T 세포 항원을 발현하는 이. 콜라이를 포함하는 푸울을 각각의 콜로니로 분리시킨 뒤, 유사 방식으로 재분석하여 양성군을 동정하였다.
Erdλ스크린 라이브러리의 하나의 96웰 평판으로 공여체 160 유래의 T 세포주를 스크리닝하여 총 9개의 양성군을 얻었다. 공여체 160 유래의 T 세포로 전술한 pBSK 라이브러리를 스크리닝하는 것에 관한 종래의 실험은 대부분 또는 모든 양성 클론이 TbH-9, Tb38-1 또는 MTI(미국 특허 출원 08/533,634호에 개시)이거나 이것 의 변형체일 것이라는 것을 암시하였다. 하지만, 서던 분석 결과 단지 3개의 웰만이 TbH-9, Tb38-1 및 MTI의 혼합 프로브와 하이브리드하는 것으로 나타났다. 나머지 6개 양성 웰 중 2개는 동일한 것으로 확인되었다. 분리된 2개의 클론(Y1-26C1 및 Y1-86C11이라 칭함)에 대하여 서열 분석된 5' cDNA 서열을 각각 서열 번호 135 및 136에 제시하였다. hTcc#1이라 칭한 분리된 클론의 전길이 cDNA 서열은 서열 137에 제시하고, 대응하는 추론 아미노산 서열은 서열 138에 제시하였다. 전술한 바와 같이 hTcc#1의 서열과 젠뱅크의 서열을 비교한 결과, 종래 동정된 엠. 투베르쿨로시스 MTCY07H7B.06과 약간의 상동성이 있는 것으로 확인되었다.
실시예 2
엠. 투베르쿨로시스 항원에 의한 T 세포 증식과 인터페론-γ생성 유도
재조합 엠. 투베르쿨로시스 항원이 T 세포 증식과 인터페론-γ생성을 유도하는 활성이 있는지 다음과 같이 측정하였다.
단백질은 문헌[Skeiky et al. J.Exp.Med., 1995, 181:1527-1537]에 기재된 바와 같이 IPTG로 유도하고 겔 용출로 정제하였다. 그 다음, 정제한 폴리펩티드를 PBMC 제조물에서 T 세포 증식을 유도할 수 있는지에 대하여 스크리닝하였다. PPD 피부 테스트에서 양성 반응을 보인다고 알려지고 그 T 세포가 PPD에 대해 반응하여 증식하는 것으로 알려진 PBMC를 10%의 수집된 인간 혈청과 젠타마이신 50 ㎍/㎖이 보강된 RPMI 1640을 포함하는 배지에서 배양하였다. 정제된 폴리펩티드를 0.5∼10 ㎍/㎖의 농도로 첨가하는 것을 2중으로 실시하였다. 96웰 둥근바닥 평판에서 200 ㎕의 부피로 배양한지 6일 후, 각 웰로부터 배지 50 ㎕를 취하여 하기하는 바와 같 이 IFN-γ농도를 측정하였다. 그 다음, 이 평판을 삼중수소화된 티미딘 1 μCi/웰로 18 시간 동안 펄스시키고, 수거한 뒤, 삼중수소의 흡수율을 가스 신틸레이션 계수기로 측정하였다. 2중의 실시 모두에서의 증식이 배지 단독물에서 배양된 세포에서 관찰되는 증식의 3배 이상인 분획을 양성으로 간주하였다.
IFN-γ는 효소 결합 면역흡착 분석법(ELISA)을 이용하여 측정하였다. PBS 중에 함유된 인간 IFN-γ에 대해 지향성인 마우스 모노클로널 항체(미국 캘리포니아주 산디에고에 소재하는 PharMingen 제품)로 ELISA 평판을 실온에서 4 시간 동안 코팅시켰다. 그 다음, 웰을 5%(W/V) 탈지 분유 함유의 PBS로 실온에서 1 시간 동안 차단시켰다. 이 평판을 PBS/0.2% TWEEN-20으로 6회 세척하고, ELISA 평판 내에서 배양 배지로 1:2로 희석한 시료를 실온에서 하룻밤 동안 항온처리하였다. 이 평판을 다시 세척하고, PBS/10% 정상 염소 혈청으로 1:3000배 희석된 폴리클로널 토끼 항인간 IFN-γ혈청을 각 웰에 첨가하였다. 그 다음 이 평판을 실온에서 2 시간 동안 항온처리하고 세척한 뒤, 양고추냉이 퍼옥시다제에 결합된 항토끼 IgG(미국 미주리주 세인트 루이스에 소재하는 시그마 케미컬 컴퍼니 제품)를 PBS/5% 탈지분유 중의 1:2000 희석물로 첨가하였다. 실온에서 2시간 동안 항온처리한 후, 평판을 세척하고 TMB 기질을 첨가하였다. 이 반응을 20분 후 1 N 황산을 첨가하여 중단시켰다. 기준 파장을 570 nm로 하고, 450 nm에서 흡광도를 측정하였다. 2중의 테스트 배양물에서 배양된 세포의 평균 OD가 배지 단독물에서만 배양된 세포의 평균 OD에 비하여 2배 이상이고 표준 편차가 3으로 나타난 분획은 양성인 것으로 간주하였다.
실시예 3
마우스 엠. 투베르쿨로시스 모델로부터 생성된 CD4+ T 세포주를 이용한 엠. 투베르쿨로시스 폴리펩티드의 정제 및 특성 규명
C57BL/6 마우스를 엠. 투베르쿨로시스로 감염시키면 약 2∼3주 동안 진행성 질병이 유발된다. 그 후, 강한 예방적 T 세포 매개의 면역 반응을 유도시키면 이 질병의 진행이 중단된다. 이 감염 모델을 이용하여 예방적 엠. 투베르쿨로시스 항원을 인식할 수 있는 T 세포주를 만들었다.
구체적으로, 28일 동안 엠. 투베르쿨로시스로 감염시킨 C57BL/6 마우스로부터 비장 세포를 분리하여, 이를 전술한 바와 같이 특이적인 항-엠. 투베르쿨로시스 T 세포주를 생성하는 데 이용하였다. 이렇게 하여 얻은 CD4+ T 세포주와, C57BL/6 마우스 유래의 정상 항원 제시(비장) 세포를 함께 사용하여 전술한 엠. 투베르쿨로시스 Erdλ스크린 라이브러리를 스크리닝하였다. T 세포에 대하여 자극 효과가 큰 것으로 확인된 반응성 라이브러리 푸울 중 1가지를 선택하고, 이에 대응하는 활성 클론(Y288C10이라 칭함)을 분리하였다.
클론 Y288C10의 서열을 분석한 결과, 2개의 잠재적 유전자를 나란히 포함하는 것으로 확인되었다. 서열 분석된 상기 2가지 유전자의 cDNA 서열(mTCC#1 및 mTCC#2라 칭함)을 각각 서열 139 및 140으로 제시하고, 이에 대응하는 추론 아미노산 서열을 각각 서열 141 및 142에 제시하였다. 이 서열을 젠뱅크의 서열과 비교한 결과 엠. 투베르쿨로시스 코스미드 MTY21C12에서 종래 밝혀진 미지 서열과 동일한 것으로 나타났다. mTCC#1 및 mTCC#2의 추론 아미노산 서열은 전술한 바와 같이 종래 동정된 TbH9 단백질군의 구성원과 약간의 상동성이 있는 것으로 확인되었다.
실시예 4
합성 폴리펩티드의 합성
HPTU(O-벤조트리아졸-N,N,N',N'-테트라메틸우로늄 헥사플루오로포스페이트) 활성화와 함께 FMOC 화학을 사용하여 밀리포어 9050 펩티드 합성기로 폴리펩티드를 합성하였다. 이 펩티드의 아미노 말단에 Gly-Cys-Gly 서열을 부착하여 펩티드의 접합 또는 표지화 방법을 제공하였다. 고체 지지체로부터 펩티드의 절단은 다음과 같은 절단 혼합물, 트리플루오로아세트산:에탄디티올:티오아니솔:물:페놀 (40:1:2:2:3)을 사용하여 실시할 수 있다. 2 시간 동안 절단한 후, 펩티드를 저온의 메틸-t-부틸-에테르에서 침전시킬 수 있다. 그 다음, 펩티드 펠릿을 0.1% 트리플루오로아세트산(TFA)을 함유하는 물에 용해하고, 동결건조시킨 뒤 C18 역상 HPLC로 정제하였다. 물(0.1% TFA 함유)에 0∼60% 구배된 아세토니트릴(0.1% TFA 함유)을 사용하여 펩티드를 용출시켰다. 순수 분획을 동결건조한 후, 펩티드를 전기분무 질량 분광분석법 및 아미노산 분석법으로 특징을 규명하였다.
이상, 예시를 목적으로 본 발명의 구체적인 양태를 설명하였으나, 본 발명의 취지와 영역을 벗어나지 않는 한 다양한 변형이 이루어질 수 있음은 자명한 것이다.
본 발명에 따른 폴리펩티드는 T 세포의 증식 및 IFN-γ의 생성을 유도하는 능력에 의해 결핵 감염의 치료, 예방 또는 진단을 위한 약학 조성물 및 백신에 유용하게 사용될 수 있다.
SEQUENCE LISTING
(1) GENERAL INFORMATION:
(i) APPLICANT:
(A) NAME: Corixa Corporation
(B) STREET: Suite 200, 1124 Columbia Street
(C) CITY: Seatle
(D) STATE: Washington
(E) COUNTRY: USA
(F) POSTAL CODE (ZIP): 98104
(G) TELEPHONE: (206) 754-5830
(H) TELEFAX: (206) 754-5994
(I)TELEX:
(ii) TITLE OF INVENTION: Compounds for Immunotherapy and Diagnosis
of Tuberculosis and Methods of Their Use
(iii) NUMBER OF SEQUENCES: 144
(iv) CORRESPONDENCE ADDRESS:
(A) ADDRESSEE: Townsend and Townsend and Crew LLP
(B) STREET: Two Embarcadero Center, Eighth Floor
(C) CITY: San Francisco
(D) STATE: California
(E) COUNTRY: USA
(F) ZIP: 94111-3834
(v) COMPUTER READABLE FORM:
(A) MEDIUM TYPE: Diskette
(B) COMPUTER: IBM compatible
(C) OPERATING SYSTEM: Windows
(D) SOFTWARE: FastSEQ for Windows Version 2.0b
(vi) CURRENT APPLICATION DATA:
(A) APPLICATION NUMBER: PCT/US98/10407
(B) FILING DATE: 20-MAY-1998
(C) CLASSIFICATION:
(vii) PRIOR APLICATION DATA:
(A) APPLICATION NUMBER: US 08/859,381
(B) FILING DATE: 20-MAY-1997
(A) APPLICATION NUMBER: US 09/073,010
(B) FILING DATE: 05-MAY-1998
(viii) ATTORNEY/AGENT INFORMATION:
(A) NAME: Bastian, Kevin L.
(B) REGISTRATION NUMBER: 34,774
(C) REFERENCE/DOCKET NUMBER: 14058-87-1PC
(ix) TELECOMMUNICATION INFORMATION:
(A) TELEPHONE: (415) 576-0200
(B) TELEFAX: (415) 576-0300
(C) TELEX:
(2) INFORMATION FOR SEQ ID NO:1:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 1886 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: DNA (genomic)
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:1:
CGCTCTGGTG ACCACCAACT TCTTCGGTGT CAACACCATC CCGATCGCCC TCAACGAGGC 60
CGACTACCTG CGCATGTGGA TCCAGGCCGC CACCGTCATG AGCCACTATC AAGCCGTCGC 120
GCACGAAATC TGGTGTCTCC ATGAATANGC CAGTTCGGGA AAGCCGTGGG CCAGTATCAC 180
CACGGGTGCG CCGGGCTCAC CGGCCTCGAC CACTCGCAGT CGCACGCCGT TGGTATCAAC 240
TAACCGTNCN GTANGTGCGC CCATCGTCTC ACCAAATCAC ACCGGGCACC GGCCTGAGAA 300
GGGCTTGGGG AGCANCCAGA GGCGATTGTC GCGGGTGCTG CCGCGCATCA TTGATCGGCC 360
GGCCGGACCA NTCGGGCCTC CCTTGACGTC CGGATCNCAC TTCCTGTGCA GCTGGCATGG 420
CTACAGCTCA CAGTGACTGC CCCACGATTG CCGGCCAGGT CCAGTTCAAA TTCCGGTGAA 480
TTCGCGGACA AAAGCAGCAG GTCAACCAAC CGCAGTCAGT CGAGGGTCCC AAACGTGAGC 540
CAATCGGTGA AATGGCTTGC TGCAGTGACA CCGGTCACAG GCTTAGCCGA CAGCACCGGA 600
ATAGCTCAGG CGGGCTATAG AGTCCTATAG AAACATTTGC TGATAGAATT AACCGCTGTC 660
TTGGCGTGAT CTTGATACGG CTCGCCGTGC GACCGGTTGG CTCAGTAGCT GACCACCATG 720
TAACCCATCC TCGGCAGGTG TCTACTAAGG CGAGACACCG CATTGGTGGG GCTGCATCGC 780
AAATCGGTCC GAGCATGTAG CACTGCCGTT ATCCCGGGAT AGCAAACCAC CCGGAACCAG 840
GGCTATCCCA GTCGCTCTCC GACGGAGGCC GTTTCGCTTT CCGTTGCCCG ATAACTCCCG 900
AGTGGATATC GGCGTTATCA NATTCAGGCT TTTCTTCGCA AGGTACCGGT GTTCGCTATA 960
TTCGGATATC TCGGACGGAT AATTACTAAA ACTTCAGTGG TTTAGATAAG GCCGCCGCAA 1020
TACTTCGCCG ATCTTGCCGA GCGCAACGGA TTTCCATCGT CGGTTTTCGT CGCCTTATCA 1080
AACATGATCG GAGATAATGA CAGATCGGCC TAGCTAGGTG TTTAGCGGAC GCGATTTAGG 1140
ACAACCGAGA TTTGCTTTGC CTCGCAACCA TGAGAGCGCC CCGCTTCGAC GCCGAATCGG 1200
GTGAGTGATG GTGGGTTAGC ACAGCCCTGA TTGCGCCACC GGCGAGGTGA TTGTGCCCGC 1260
CACGAGGCCG CCGCCGGCTA GCCCCATGAG CACGNTATAT AGACTCTCCT GCAACAGATC 1320
TCATACCGAT CGAAGGCGAA GCGCAGGCAT CGACGTCGGA GACACTGCCT TGGGATCGCG 1380
CCGCCTACAC GGCGGTTGGC GCATTGTCGC AGCGCAGTTG CAGGAGGGCA AATGTGCGCA 1440
GACGATGTAG TCGACAACAA GTGNACATGC CGTCTTCACG AACTCAAAAC TGACGATCTG 1500
CTTAGCATGA AAAAAACTGT TGACATCGGC CAAGCATGAC AGCCAGACTG TAGGCCTACG 1560
CGTGCAATGC AGAACCAAGG NTATGCATGG AATCGACGAC CGTTGAGATA GGCGGCAGGC 1620
ATGAGCAGAG CGTTCATCAT CGATCCAACG ATCAGTGCCA TTGACGGCTT GTACGACCTT 1680
CTGGGGATTG GAATACCCAA CCAAGGGGGT ATCCTTTACT CCTCACTAGA GTACTTCGAA 1740
AAAGCCCTGG AGGAGCTGGC AGCAGCGTTT CCGGGTGATG GCTGGTTAGG TTCGGCCGCG 1800
GACAAATACG CCGGCAAAAA CCGCAACCAC GTGAATTTTT TCCAGGAACT GGCAGACCTC 1860
GATCGTCAGC TCATCAGCCT GATCCA 1886
(2) INFORMATION FOR SEQ ID NO:2:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 2305 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: DNA (genomic)
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:2:
GGCACGCGCT GGCCGCGCAA TACACCGAAA TTGCAACGGA ACTCGCAAGC GTGCTCGCTG 60
CGGTGCAGGC AAGCTCGTGG CAGGGGCCCA GCGCCGACCG GTTCGTCGTC GCCCATCAAC 120
CGTTCCGGTA TTGGCTAACC CACGCTGCCA CGGTGGCCAC CGCAGCAGCC GCCGCGCACN 180
AAACGGCCGC CGCCGGGTAT ACGTCCGCAT TGGGGGGCAT GCCTACGCTA GCCGAGTTGG 240
CGGCCAACCA TGCCATGCAC GGCGCTCTGG TGACCACCAA CTTCTTCGGT GTCAACACCA 300
TCCCGATCGC CCTCAACGAG GCCGACTACC TGCGCATGTG GATCCAGGCC GCCACCGTCA 360
TGAGCCACTA TCAAGCCGTC GCGCACGAAA GCGTGGCGGC GACCCCCAGC ACGCCGCCGG 420
CGCCGCAGAT AGTGACCAGT GCGGCCAGCT CGGCGGCTAG CAGCAGCTTC CCCGACCCGA 480
CCAAATTGAT CCTGCAGCTA CTCAAGGATT TCCTGGAGCT GCTGCGCTAT CTGGCTGTTG 540
AGCTGCTGCC GGGGCCGCTC GGCGACCTCA TCGCCCAGGT GTTGGACTGG TTCATCTCGT 600
TCGTGTCCGG TCCAGTCTTC ACGTTTCTCG CCTACCTGGT GCTGGACCCA CTGATCTATT 660
TCGGACCGTT CGCCCCGCTG ACGAGTCCGG TCCTGTTGCC TGCTGTGGAG TTACGCAACC 720
GCCTCAAAAC CGCCACCGGA CTGACGCTGC CACCTACCGT GATTTTCGAT CATCCCACTC 780
CCACTGCGGT CGCCGAGTAT GTCGCCCAGC AAATGTCTGG CAGCCGCCCA ACGGAATCCG 840
GTGATCCGAC GTCGCAGGTT GTCGAACCCG CTCGTGCCGA ATTCGGCACG AGTGCTGTTC 900
ATCAAATCCC CCCGAGACCT GCGGACACCC GGCGCGCTTG CCGACATCGA GATGATGTCC 960
CGCGAGATAG CAGAATTGCC CAACATCGTG ATGGTGCGGG GCTTGACCCG ACCGAACGGG 1020
GAACCTCTGA AGGAGACCAA GGTCTCGTTT CAGGCTGGTG AAGTGGGCGG CAAGCTCGAC 1080
GAAGCGACCA CCCTGCTCGA AGAGCACGGA GGCGAGCTGG ACCAGCTGAC CGGCGGTGCG 1140
CACCAGTTGG CCGACGCCCT CGCCCAAATA CGCAACGAAA TCAATGGGGC CGTGGCCAGC 1200
TCGAGCGGGA TAGTCAACAC CCTGCAGGCC ATGATGGACC TGATGGGCGG TGACAAGACC 1260
ATCCGACAAC TGGAAAATGC GTCCCAATAT GTCGGGCGCA TGCGGGCTCT GGGGGACAAT 1320
CTGAGCGGGA CCGTCACCGA TGCCGAACAA ATCGCCACTT GGGCCAGCCC TATGGTCAAC 1380
GCCCTCAACT CCAGCCCGGT GTGTAACAGC GATCCCGCCT GTCGGACGTC GCGCGCACAG 1440
TTGGCGGCGA TTGTCCAGGC GCAGGACGAC GGCCTGCTCA GGTCCATCAG AGCGCTAGCC 1500
GTCACCCTGC AACAGACGCA GGAATACCAG ACACTCGCCC GGACGGTGAG CACACTGGAC 1560
GGGCAACTGA AGCAAGTCGT CAGCACCCTC AAAGCGGTCG ACGGCCTACC CACCAAATTG 1620
GCTCAAATGC AGCAAGGAGC CAACGCTCTC GCCGACGGCA GCGCAGCGCT GGCGGCAGGC 1680
GTGCAGGAAT TGGTCGATCA GGTCAAAAAG ATGGGCTCAG GGCTCAACGA GGCCGCCGAC 1740
TTCCTGTTGG GGATCAAGCG GGATGCGGAC AAGCCGTCAA TGGCGGGCTT CAACATTCCA 1800
CCGCAGATTT TTTCGAGGGA CGAGTTCAAG AAGGGCGCCC AGATTTTCCT GTCGGCCGAT 1860
GGTCATGCGG CGCGGTACTT CGTGCAGAGC GCGCTGAATC CGGCCACCAC CGAGGCGATG 1920
GATCAGGTCA ACGATATCCT CCGTGTTGCG GATTCCGCGC GACCGAATAC CGAACTCGAG 1980
GATGCCACGA TAGGTCTGGC GGGGGTTCCG ACTGCGCTGC GGGATATCCG CGACTACTAC 2040
AACAGCGATA TGAAATTCAT CGTCATTGCG ACGATCGTTA TCGTATTCTT GATTCTCGTC 2100
ATTCTGNTGC GCGCACTTGT GGNTCCGATA TATCTGATAG GCTCGGTGCT GATTTCTTAC 2160
TTGTCGGCCC TAGGCATAGG AACTTTCGTT TTCCAATTGA TACTGGGCCA GGAAATGCAT 2220
TGGAGCCTGC CGGGACTGTC CTTCATATTA TTGGTTGCCA TCGGCGCTGA CTACAACATG 2280
CTGCTCATTT CACGCATCCG CGACG 2305
(2) INFORMATION FOR SEQ ID NO:3:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 1742 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: DNA (genomic)
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:3:
CCGCTCTCTT TCAACGTCAT AAGTTCGGTG GGCCAGTCGG CCGCGCGTGC ATATGGCACC 60
AATAACGCGT GTCCCATGGA TACCCGGACC GCACGACGGT AGAGCGGATC AGCGCAGCCG 120
GTGCCGAACA CTACCGCGTC CACGCTCAGC CCTGCCGCGT TGCGGAAGAT CGAGCCCAGG 180
TTCTCATGGT CGTTAACGCC TTCCAACACT GCGACGGTGC GCGCCCCGGC GACCACCTGA 240
GCAACGCTCG GCTCCGGCAC CCGGCGCGCG GCTGCCAACA CCCCACGATT GAGATGGAAG 300
CCGATCACCC GTGCCATGAC ATCAGCCGAC GCTCGATAGT ACGGCGCGCC GACACCGGCC 360
AGATCATCCT TGAGCTCGGC CAGCCGGCGG TCGGTGCCGA ACAGCGCCAG CGGCGTGAAC 420
CGTGAGGCCA GCATGCGCTG CACCACCAGC ACACCCTCGG CGATCACCAA CGCCTTGCCG 480
GTCGGCAGAT CGGGACNACN GTCGATGCTG TTCAGGTCAC GGAAATCGTC GAGCCGTGGG 540
TCGTCGGGAT CGCAGACGTC CTGAACATCG AGGCCGTCGG GGTGCTGGGC ACAACGGCCT 600
TCGGTCACGG GCTTTCGTCG ACCAGAGCCA GCATCAGATC GGCGGCGCTG CGCAGGATGT 660
CACGCTCGCT GCGGTTCAGC GTCGCGAGCC GCTCAGCCAG CCACTCTTGC AGAGAGCCGT 720
TGCTGGGATT AATTGGGAGA GGAAGACAGC ATGTCGTTCG TGACCACACA GCCGGAAGCC 780
CTGGCAGCTG CGGCGGCGAA CCTACAGGGT ATTGGCACGA CAATGAACGC CCAGAACGCG 840
GCCGCGGCTG CTCCAACCAC CGGAGTAGTG CCCGCAGCCG CCGATGAAGT ATCAGCGCTG 900
ACCGCGGCTC AGTTTGCTGC GCACGCGCAG ATGTACCAAA CGGTCAGCGC CCAGGCCGCG 960
GCCATTCACG AAATGTTCGT GAACACGCTG GTGGCCAGTT CTGGCTCATA CGCGGCCACC 1020
GAGGCGGCCA ACGCAGCCGC TGCCGGCTGA ACGGGCTCGC ACGAACCTGC TGAAGGAGAG 1080
GGGGAACATC CGGAGTTCTC GGGTCAGGGG TTGCGCCAGC GCCCAGCCGA TTCAGNTATC 1140
GGCGTCCATA ACAGCAGACG ATCTAGGCAT TCAGTACTAA GGAGACAGGC AACATGGCCT 1200
CACGTTTTAT GACGGATCCG CATGCGATGC GGGACATGGC GGGCCGTTTT GAGGTGCACG 1260
CCCAGACGGT GGAGGACGAG GCTCGCCGGA TGTGGGCGTC CGCGCAAAAC ATTTCCGGTG 1320
CGGGCTGGAG TGGCATGGCC GAGGCGACCT CGCTAGACAC CATGACCTAG ATGAATCAGG 1380
CGTTTCGCAA CATCGTGAAC ATGCTGCACG GGGTGCGTGA CGGGCTGGTT CGCGACGCCA 1440
ACAANTACGA ACAGCAAGAG CAGGCCTCCC AGCAGATCCT GAGCAGNTAG CGCCGAAAGC 1500
CACAGCTGNG TACGNTTTCT CACATTAGGA GAACACCAAT ATGACGATTA ATTACCAGTT 1560
CGGGGACGTC GACGCTCATG GCGCCATGAT CCGCGCTCAG GCGGCGTCGC TTGAGGCGGA 1620
GCATCAGGCC ATCGTTCGTG ATGTGTTGGC CGCGGGTGAC TTTTGGGGCG GCGCCGGTTC 1680
GGTGGCTTGC CAGGAGTTCA TTACCCAGTT GGGCCGTAAC TTCCAGGTGA TCTACGAGCA 1740
GG 1742
(2) INFORMATION FOR SEQ ID NO:4:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 2836 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: DNA (genomic)
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:4:
GTTGATTCCG TTCGCGGCGC CGCCGAAGAC CACCAACTCC GCTGGGGTGG TCGCACAGGC 60
GGTTGCGTCG GTCAGCTGGC CGAATCCCAA TGATTGGTGG CTCNGTGCGG TTGCTGGGCT 120
CGATTACCCC CACGGAAAGG ACGACGATCG TTCGTTTGCT CGGTCAGTCG TACTTGGCGA 180
CGGGCATGGC GCGGTTTCTT ACCTCGATCG CACAGCAGCT GACCTTCGGC CCAGGGGGCA 240
CAACGGCTGG CTCCGGCGGA GCCTGGTACC CAACGCCACA ATTCGCCGGC CTGGGTGCAG 300
GCCCGGCGGT GTCGGCGAGT TTGGCGCGGG CGGAGCCGGT CGGGAGGTTG TCGGTGCCGC 360
CAAGTTGGGC CGTCGCGGCT CCGGCCTTCG CGGAGAAGCC TGAGGCGGGC ACGCCGATGT 420
CCGTCATCGG CGAAGCGTCC AGCTGCGGTC AGGGAGGCCT GCTTCGAGGC ATACCGCTGG 480
CGAGAGCGGG GCGGCGTACA GGCGCCTTCG CTCACCGATA CGGGTTCCGC CACAGCGTGA 540
TTACCCGGTC TCCGTCGGCG GGATAGCTTT CGATCCGGTC TGCGCGGCCG CCGGAAATGC 600
TGCAGATAGC GATCGACCGC GCCGGTCGGT AAACGCCGCA CACGGCACTA TCAATGCGCA 660
CGGCGGGCGT TGATGCCAAA TTGACCGTCC CGACGGGGCT TTATCTGCGG CAAGATTTCA 720
TCCCCAGCCC GGTCGGTGGG CCGATAAATA CGCTGGTCAG CGCGACTCTT CCGGCTGAAT 780
TCGATGCTCT GGGCGCCCGC TCGACGCCGA GTATCTCGAG TGGGCCGCAA ACCCGGTCAA 840
ACGCTGTTAC TGTGGCGTTA CCACAGGTGA ATTTGCGGTG CCAACTGGTG AACACTTGCG 900
AACGGGTGGC ATCGAAATCA ACTTGTTGCG TTGCAGTGAT CTACTCTCTT GCAGAGAGCC 960
GTTGCTGGGA TTAATTGGGA GAGGAAGACA GCATGTCGTT CGTGACCACA CAGCCGGAAG 1020
CCCTGGCAGC TGCGGCGGCG AACCTACAGG GTATTGGCAC GACAATGAAC GCCCAGAACG 1080
CGGCCGCGGC TGCTCCAACC ACCGGAGTAG TGCCCGCAGC CGCCGATGAA GTATCAGCGC 1140
TGACCGCGGC TCAGTTTGCT GCGCACGCGC AGATGTACCA AACGGTCAGC GCCCAGGCCG 1200
CGGCCATTCA CGAAATGTTC GTGAACACGC TGGTGGCCAG TTCTGGCTCA TACGCGGCCA 1260
CCGAGGCGGC CAACGCAGCC GCTGCCGGCT GAACGGGCTC GCACGAACCT GCTGAAGGAG 1320
AGGGGGAACA TCCGGAGTTC TCGGGTCAGG GGTTGCGCCA GCGCCCAGCC GATTCAGCTA 1380
TCGGCGTCCA TAACAGCAGA CGATCTAGGC ATTCAGTACT AAGGAGACAG GCAACATGGC 1440
CTCACGTTTT ATGACGGATC CGCATGCGAT GCGGGACATG GCGGGCCGTT TTGAGGTGCA 1500
CGCCCAGACG GTGGAGGACG AGGCTCGCCG GATGTGGGCG TCCGCGCAAA ACATTTCCGG 1560
TGCGGGCTGG AGTGGCATGG CCGAGGCGAC CTCGCTAGAC ACCATGACCT AGATGAATCA 1620
GGCGTTTCGC AACATCGTGA ACATGCTGCA CGGGGTGCGT GACGGGCTGG TTCGCGACGC 1680
CAACAACTAC GAACAGCAAG AGCAGGCCTC CCAGCAGATC CTGAGCAGCT AGCGCCGAAA 1740
GCCACAGCTG CGTACGCTTT CTCACATTAG GAGAACACCA ATATGACGAT TAATTACCAG 1800
TTCGGGGACG TCGACGCTCA TGGCGCCATG ATCCGCGCTC AGGCGGCGTC GCTTGAGGCG 1860
GAGCATCAGG CCATCGTTCG TGATGTGTTG GCCGCGGGTG ACTTTTGGGG CGGCGCCGGT 1920
TCGGTGGCTT GCCAGGAGTT CATTACCCAG TTGGGCCGTA ACTTCCAGGT GATCTACGAG 1980
CAGGCCAACG CCCACGGGCA GAAGGTGCAG GCTGCCGGCA ACAACATGGC GCAAACCGAC 2040
AGCGCCGTCG GCTCCAGCTG GGCCTAAAAC TGAACTTCAG TCGCGGCAGC ACACCAACCA 2100
GCCGGTGTGC TGCTGTGTCC TGCAGTTAAC TAGCACTCGA CCGCTGAGGT AGCGATGGAT 2160
CAACAGAGTA CCCGCACCGA CATCACCGTC AACGTCGACG GCTTCTGGAT GCTTCAGGCG 2220
CTACTGGATA TCCGCCACGT TGCGCCTGAG TTACGTTGCC GGCCGTACGT CTCCACCGAT 2280
TCCAATGACT GGCTAAACGA GCACCCGGGG ATGGCGGTCA TGCGCGAGCA GGGCATTGTC 2340
GTCAACGACG CGGTCAACGA ACAGGTCGCT GCCCGGATGA AGGTGCTTGC CGCACCTGAT 2400
CTTGAAGTCG TCGCCCTGCT GTCACGCGGC AAGTTGCTGT ACGGGGTCAT AGACGACGAG 2460
AACCAGCCGC CGGGTTCGCG TGACATCCCT GACAATGAGT TCCGGGTGGT GTTGGCCCGG 2520
CGAGGCCAGC ACTGGGTGTC GGCGGTACGG GTTGGCAATG ACATCACCGT CGATGACGTG 2580
ACGGTCTCGG ATAGCGCCTC GATCGCCGCA CTGGTAATGG ACGGTCTGGA GTCGATTCAC 2640
CACGCCGACC CAGCCGCGAT CAACGCGGTC AACGTGCCAA TGGAGGAGAT CTCGTGCCGA 2700
ATTCGGCACG AGGCACGAGG CGGTGTCGGT GACGACGGGA TCGATCACGA TCATCGACCG 2760
GCCGGGATCC TTGGCGATCT CGTTGAGCAC GACCCGGGCC CGCGGGAAGC TCTGCGACAT 2820
CCATGGGTTC TTCCCG 2836
(2) INFORMATION FOR SEQ ID NO:5:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 900 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: DNA (genomic)
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:5:
AACATGCTGC ACGGGGTGCG TGACGGGCTG GTTCGCGACG CCAACAACTA CGAGCAGCAA 60
GAGCAGGCCT CCCAGCAGAT CCTCAGCAGC TAACGTCAGC CGCTGCAGCA CAATACTTTT 120
ACAAGCGAAG GAGAACAGGT TCGATGACCA TCAACTATCA GTTCGGTGAT GTCGACGCTC 180
ACGGCGCCAT GATCCGCGCT CAGGCCGGGT TGCTGGAGGC CGAACATCAG GCCATCATTC 240
GTGATGTGTT GACCGCGAGT GACTTTTGGG GCGGCGCCGG TTCGGCGGCC TGCCAGGGGT 300
TCATTACCCA ATTGGGCCGT AACTTCCAGG TGATCTACGA ACAGGCCAAC GCCCACGGGC 360
AGAAGGTGCA GGCTGCCGGC AACAACATGG CGCAAACCGA CAGCGCCGTC GGCTCCAGCT 420
GGGCCTGACA CCAGGCCAAG GCCAGGGACG TGGTGTACGA GTGAAGGTTC CTCGCGTGAT 480
CCTTCGGGTG GCAGTCTAGG TGGTCAGTGC TGGGGTGTTG GTGGTTTGCT GCTTGGCGGG 540
TTCTTCGGTG CTGGTCAGTG CTGCTCGGGC TCGGGTGAGG ACCTCGAGGC CCAGGTAGCG 600
CCGTCCTTCG ATCCATTCGT CGTGTTGTTC GGCGAGGACG GCTCCGACGA GGCGGATGAT 660
CGAGGCGCGG TCGGGGAAGA TGCCCACGAC GTCGGTTCGG CGTCGTACCT CTCGGTTGAG 720
GCGTTCCTGG GGGTTGTTGG ACCAGATTTG GCGCCAGATC TTCTTGGGGA AGGCGGTGAA 780
CGCCAGCAGG TCGGTGCGGG CGGTGTCGAN GTGCTCGGCC ACCGCGGGGA GTTTGTCGGT 840
CAGAGCGTCG AGTACCCGAT CATATTGGGC AACAACTGAT TCGGCGTTGG GCTGGTCGTA 900
(2) INFORMATION FOR SEQ ID NO:6:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 1905 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: DNA (genomic)
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:6:
GCTCGCCGGA TGTGGGCGTC CGCGCAAAAC ATTTCCGGTG CGGGCTGGAG TGGCATGGCC 60
GAGGCGACCT CGCTAGACAC CATGGCCCAG ATGAATCAGG CGTTTCGCAA CATCGTGAAC 120
ATGCTGCACG GGGTGCGTGA CGGGCTGGTT CGCGACGCCA ACAACTACGA GCAGCAAGAG 180
CAGGCCTCCC AGCAGATCCT CAGCAGCTAA CGTCAGCCGC TGCAGCACAA TACTTTTACA 240
AGCGAAGGAG AACAGGTTCG ATGACCATCA ACTATCAGTT CGGTGATGTC GACGCTCACG 300
GCGCCATGAT CCGCGCTCAG GCCGGGTTGC TGGAGGCCGA GCATCAGGCC ATCATTCGTG 360
ATGTGTTGAC CGCGAGTGAC TTTTGGGGCG GCGCCGGTTC GGCGGCCTGC CAGGGGTTCA 420
TTACCCAGTT GGGCCGTAAC TTCCAGGTGA TCTACGAACA AGCCAACACC CACGGGCAGA 480
AGGTGCAAGC TGCCGGCAAC AACATGGCGC AAACCGACAG CGCCGTCNGC TCCAGCTGGG 540
CCTGACACCA GGCCAAGGCC AGGGACGTGG TGTACNAGTG AAGGTTCCTC GCGTGATCCT 600
TCGGGTGGCA GTCTAGGTGG TCAGTGCTGG GGTGTTGGTG GTTTGCTGCT TGGCGGGTTC 660
TTCGGTGCTG GTCAGTGCTG CTCGGGCTCG GGTGAGGACC TCGAGGCCCA GGTAGCGCCG 720
TCCTTCGATC CATTCGTCGT GTTGTTCGGC GAGGACNGCT CCGACGANGC GGATGATCGA 780
GGCGCGGTCG GGGAAGATGC CCACGACGTC GGTTCGGCGT CGTACCTCTC GGTTGAAGCG 840
TTCCTGGGGG CCACCGCTTG GCGCCNANGC ACTCCACGCC AATTCGTCNC ACCTAACAGC 900
GGTGGCCAAC GACTATGACT ACGACACCGT TTTTGCCAGG GCCCTCNAAA GGATCTGCGC 960
GTCCCGGCGA CACGCTTTTT GCGATAAGTA CCTCCGGCAA TTCTATGAGT GTACTGCGGN 1020
CCGCGAAAAC CGCAAGGGAG TTGGGTGTGA CGGTTNTTGC AAATGACGGG CGAATCCGGC 1080
GGCCAGCTGG CAGAATTCGC AGATTTCTTG ATCAACGTCC CGTCACGCGA CACCGGGCGA 1140
ATCCAGGAAT CTCACATCGT TTTTATTCAT GCGATCTCCG AACATGTCGA ACACGCGCTT 1200
TTCGCGCCTC GCCAATAGGA AAGCCGATCC TTACGCGGCC ATTCGAAAGA TGGTCGCGGA 1260
ACGTGCGGGA CACCAATGGT GTCTCTTCCT CGATAGAGAC GGGGTCATCA ATCGACAAGT 1320
GGTCGGCGAC TACGTACGGA ACTGGCGGCA GTTTGAATGG TTGCCCGGGG CGGCGCGGGC 1380
GTTGAAGAAG CTACGGGCAT GGGCTCCGTA CATCGTTGTC GTGACAAACC AGCAGGGCGT 1440
GGGTGCCGGA TTGATGAGCG CCGTCGACGT GATGGTGATA CATCGGCACC TCCAAATGCA 1500
GCTTGCATCC GATGGCGTGC TGATAGATGG ATTTCAGGTT TGCCCGCACC ACCGTTCGCA 1560
GCGGTGTGGC TGCCGTAAGC CGAGACCGGG TCTGGTCCTC GACTGGCTCG GACGACACCC 1620
CGACAGTGAG CCATTGCTGA GCATCGTGGT TGGGGACAGC CTCAGCGATC TTGACATTGG 1680
CACACAACGT CGCCGCTGCT GCCGGTGCAT GTGCCAGTGT CCAGATAGGG GGCGCCAGTT 1740
CTGGCGGTGT CGCTGACGCG TCATTTGACT CGCTCTGGGA GTTCGCTGTC GCAGTCGGAC 1800
ATGCGCGGGG GGAGCGGGGC TAATGGCGAT CTTGCGCGGG CGAGCGCCGT NGCGGNTCGG 1860
ACTNNGCGGT GGCGGGACAG ACGTGGAACC GTACTCGAGC CAGTT 1905
(2) INFORMATION FOR SEQ ID NO:7:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 2921 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: DNA (genomic)
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:7:
CGGGATGCCG TGGTGGTTGG TATTGCCCAA ACCCTGGCGC TGGTCCCCGG GGTATCCAGG 60
TCCGGGTCGA CCATCAGCGC TGGACTGTTT CTCGGACTCG ACCGTGAACT GGCCGCCCGA 120
TTCGGATTCC TGCTGGCCAT TCCAGCGGTG TTCGCCTCCG GGTTGTTCTC GTTGCCCGAC 180
GCATTCCACC CGGTAACCGA GGGCATGAGC GCTACTGGCC CGCAGTTGCT GGTGGCCACC 240
CTGATCGCGT TCGTCCTCGG TCTGACCGCG GTGGCCTGGC TGCTGCGGTT TCTGGTGCGA 300
CACAACATGT ACTGGTTCGT CGGCTACCGG GTGCTCGTCG GGACGGGCAT GCTCGTGCTG 360
CTGGCTACCG GGACGGTAGC CGCGACATGA CCGTCATCTT GCTACGCCAT GCCCGTTCCA 420
CCTCGAACAC CGCGGGCGTG CTGGCCGGCC GGTCCGGCGT CGACCTCGAC GAGAAGGGGC 480
GCGAGCAGGC CACCGGGTTG ATCGATCGAA TTGGTGACCT GCCGATCCGG GCGGTCGCGT 540
CTTCTCCAAT GCTGCGGTGT CAACGCACCG TCGAACCGCT GGCCGAGGCG CTGTGCCTGG 600
AGCCGCTCAT CGATGACCGG TTCTCCGAAG TCGACTACGG CGAATGGACT GGCAGAAAAA 660
TCGGTGACCT GGTCGACGAG CCGTTGTGGC GGGTAGTCCA GGCCCACCCC AGCGCGGCGG 720
TGTTTCCCGG CGGTGAGGGT TTGGCGCAGG TGCAGACGTG GTTGTCCTGA CGGATTTCCA 780
TGCCGGGGAA CACCAAGACC GGATCGGCAC TGGCGGTCGC CGGCGAAAAC CCGGCCGCCA 840
ATAGGGCGAC CGTCGCTGCG AATGCGCGTG GTACCAGGCG GACCACCTTG AACTCCCATC 900
CGTCGGGGCC AAGCGCATCG CCCGCCGCCG GTTACGGCTA AGGCGTACCA AAACCCGACG 960
GTAATACTTC GGCAATGTCG GGTCNCGACG TTACCGAGAC GTGACCAGNG AGGCNGCGGC 1020
ATTGGATTTA TCGATGGTGC GCGGTTCCCA NCCCGGCGGT CCGAANACGT AGCCCAGCCG 1080
ATCCCGCAGA CGTGTTGCCG ACCGCCAGTC ACGCACGATC GCCACGTACT CGCGGGTCTG 1140
CAGCTTCCAG ATGTTGAACG TGTCGACCCG CTTGGTCAGG CCATAATGCG GTCGGAATAG 1200
CTCCGGCTGA AAGCTACCGA ACAGGCGGTC CCAGATGATG AGGATGCCGC CATAGTTCTT 1260
GTCCANATAC ACCGGGTCCA TTCCGTGGTG GACCCGGTGG TGCGACGGGG TATTGAAGAC 1320
GAATTCGAAC CACCGCGGCA GCCTGTCGAT CCGCTCGGTG TGCACCCAGA ACTGGTAGAT 1380
CAAGTTCAGC GACCAATTGC AGAACACCAT CCAAGGGGGA AGCCCCATCA GTGGCAGCGG 1440
AACCCACATG AGAATCTCGC CGCTGTTGTT CCANTTTCTG GCGCAGCGCG GTGGCGAAGT 1500
TGAAGTATTC GCTGGAGTGA TGCGCCTGGT GGGTAGCCCA GATCAGCCGA ACTCGGTGGG 1560
CGATGCGGTG ATAGGAGTAG TACAGCAGAT CGACACCAAC GATCGCGATC ACCCAGGTGT 1620
ACCACCGGTG GGCGGACAGC TGCCAGGGGG CAAGGTAGGC ATAGATTGCG GCATAACCGA 1680
GCAGGGCAAG GGACTTCCAG CCGGCGGTGG TGGCTATCGA AACCAGCCCC ATCGAGATGC 1740
TGGCCACCGA GTCGCGGGTG AGGTAAGCGC CCGAGGCGGG CCGTGGCTGC CCGGTAGCAG 1800
CGGTCTCGAT GCTTTCCAGC TTGCGGGCCG CCGTCCATTC GAGAATCAGC AGCAATAGAA 1860
AACATGGAAT GGCGAACAGT ACCGGGTCCC GCATTTCCTC GGGCAGCGCT GAGAAGAATC 1920
CGGCGACGGC ATGGCCGAGG CGACCTCGNT AGACACCATG ACCCAGATGA ATCAGGCGTT 1980
TCGCAACATC GTGAACATGC TGCACGGGGT GCGTGACGGG CTGGTTCGCG ACGCCAACAA 2040
NTACGAACAG CAAGAGCAGG CCTCCCAGCA GATCCTCAGC AGCTGACCCG GCCCGACGAC 2100
TCAGGAGGAC ACATGACCAT CAACTATCAA TTCGGGGACG TCGACGCTCA CGGCGCCATG 2160
ATCCGCGCTC AGGCCGGGTC GCTGGAGGCC GAGCATCAGG CCATCATTTC TGATGTGTTG 2220
ACCGCGAGTG ACTTTTGGGG CGGCGCCGGT TCGGCGGCCT GCCAGGGGTT CATTACCCAG 2280
CTGGGCCGTA ACTTCCAGGT GATNTACGAG CAGGCCAACG CCCACGGGCA GAAGGTGCAG 2340
GCTGCCGGCA ACAACATGGC ACAAACCGAC AGCGCCGTCG GCTCCAGCTG GGCATAAAGN 2400
TGGCTTAAGG CCCGCGCCGT CAATTACAAC GTGGCCGCAC ACCGGTTGGT GTGTGGCCAC 2460
GTTGTTATCT GAACGACTAA CTACTTCGAC CTGCTAAAGT CGGCGCGTTG ATCCCCGGTC 2520
GGATGGTGCT GAACTGGGAA GATGGCCTCA ATGCCCTTGT TGCGGAAGGG ATTGAGGCCA 2580
TCGTGTTTCG TACTTTAGGC GATCAGTGCT GGTTGTGGGA GTCGCTGCTG CCCGACGAGG 2640
TGCGCCGACT GCCCGAGGAA CTGGCCCGGG TGGACGCATT GTTGGACGAT CCGGCGTTCT 2700
TCGCCCCGTT CGTGCCGTTC TTCGACCCGC GCAGGGGCCG GCCGTCGACG CCGATGGAGG 2760
TCTATCTGCA GTTGATGTTT GTGAAGTTCC GCTACCGGCT GGGCTATGAG TCGCTGTGCC 2820
GGGAGGTGGC TGATTCGATC ACCTGACGGC GGTTTTGCCG CATTGCGCTG GACGGGTCGG 2880
TGCCGCATCC GACCACATTG ATGAAGCTCA CCACGCGTTG C 2921
(2) INFORMATION FOR SEQ ID NO:8:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 1704 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: DNA (genomic)
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:8:
CGCGATCGTC GTCAACGANG TCGACCGTCA CCACGGACTG ATCAACAAGT TCGCAGGCGA 60
CGCCGCCCTG GCCATCTTCG GAGCCCCGAA CCGCCTCGAC CGTCCCGAAG ACGCCGCGCT 120
GGCCGCCGCC CGGGCCATAN CCGANCGGCT GGCCNACGAG ATGCCCGAGG TCCAAGCCGG 180
CATCGGGGTG GCGGCAGGCC ANATCGTCGC CGGCAATGTC GGCGCCAAGC AAAGATTCNA 240
ATACACAGTG GTCGGCAAGC CGGTCAACCA NGCGGCCCGA TTGTGCGAAC TGGCCAAATC 300
ACACCCCGCG CGATTGGGTC TCGCCCGCTC GGCTCATGGT CACCCAATTC AAGGACTACT 360
TTGGCCTGGC GCACGACCTG CCGAAGTGGG CGAGTGAAGG CGCCAAAGCC GCCGGTGAGG 420
CCGCCAAGGC GTTGCCGGCC GCCGTTCCGG CCATTCCGAG TGCTGGCCTG AGCGGCGTTG 480
CGGGCGCCGT CGGTCAGGCG GCGTCGGTCG GGGGATTGAA GGTTCCGGCC GTTTGGACCG 540
CCACGACCCC GGCGGCGAGC CCCGCGGTGC TGGCGGCGTC CAACGGCCTC GGAGCCGCGG 600
CCGCCGCTGA AGGTTCGACA CACGCGTTTG GCGGGATGCC GCTCATGGGT ANCGGTGCCG 660
GACGTGCGTT TAACAACTTC GCTGCCCCTC GATACGGATT CAAGCCGACC GTGATCGCCC 720
AACCGCCGGC TGGCGGATGA CCAACTACGT TCGTTGATCG AGGATCGAAT TCNACGATTC 780
AAAGGGAGGA ATTCATATGA CCTCNCGTTT TATGACGGAT CCGCACGCNA TNCGGGACAT 840
GGCGGGCCGT TTTGAGGTGC ACGCCCAGAC GGTGGAGGAC GAGGCTNGCN GGATGTGGGC 900
GTCCGCGCAA AACATTTCCG GTGCGGGCTG GAGTGGCATG GCCGAGGCGA CCTCGNTAGA 960
CACCATGGCC CAGATGAATC AGGCGTTTCN CAACATCGTG AACATGCTGC ACGGGGTGNG 1020
TGACGGGCTG GTTCGCGACG CCAACAACTA CGAACAGCAA GAGCAGGCCT CCCAGCAGAT 1080
CCTCAGCAGC TGACCCGGCC CGACGACTCA GGAGGACACA TGACCATCAA CTATCAATTC 1140
GGGGACGTCG ACGCTCATGG CGCCATGATC CGCGCTNTGG CCGGGTTGCT GGAGGCCGAG 1200
CATCAGGCCA TCATTTCTGA TGTGTTGACC GCGAGTGACT TTTGGGGCGG CGCCGGTTCG 1260
GCGGCCTGCC AGGGGTTCAT TACCCAGTTG GGCCGTAACT TCCAGGTGAT TTACGAGCAG 1320
GCCAACGCCC ACGGGCAGAA GGTGCAGGCT GCCGGCAACA ACATGGCACA AACCGACAGC 1380
GCCGTNGGNT CCAGCTGGGC CTAACCCGGG TCNTAAGTTG GGTCCGCGCA GGGCGGGCCG 1440
ATCAGCGTNG ACTTTGGCGC CCGATACACG GGCATNTTNT NGTCGGGAAC ACTGCGCCCG 1500
CGTCAGNTGC CCGCTTCCCC TTGTTNGGCG ACGTGCTCGG TGATGGCTTT GACGACCGCT 1560
TCGCCGGCGC GGCCAATCAA TTGGTCGCGC TTGCCTNTAG CCCATTCGTG CGACGCCCGC 1620
GGCGCCGCGA GTTGTCCCTT GAAATAAGGA ATCACAGCAC GGGCGAACAG CTCATAGGAG 1680
TGAAAGGTTG CCGTGGCGGG GCCC 1704
(2) INFORMATION FOR SEQ ID NO:9:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 2286 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: DNA (genomic)
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:9:
CCGTCTTGGC GTCTGGGCGC ATTGTGATCT GGGCCANTTG CCCCTCCACC CAGACCGCGC 60
CCAGCTTGTC GATCCAGCCC GCGACCCGGA TTGCCACCGC GCGAACCGGG AACGGATTCT 120
CCGCTGAATT CTGGGTCACT TCGCAGTCGC GCGGGTGATC CTGTTGGCGA NCAGCGTCTG 180
GAACGGGCGT CNAACGCGTG CCGTAAGCCC AGCGTGTACG CCGTCAGCCC GACGCCGATG 240
CCGAATGCCT TGCCGCCCAA GCTGAGCCGC GCGGGCTCCA CCAAGAGCGT CACGGTGAGC 300
CAGCCAACCA GATGCAAGGC GACGATCACC GCGAAGTGCC GAATTCGGCA CGAGAGGTGC 360
TGGAAATCCA GCAATACGCC CGCGAGCCGA TCTCGTTGGA CCAGACCATC GGCGACGANG 420
GCGACAGNCA GCTTGGCGAT TTCATCGAAA ACAGCGAGGC GGTGGTGGNC GTCGACGCGG 480
TGTCCTTCAC TTTGCTGCAT GATCAACTGC ANTCGGTGCT GGACACGCTC TCCGAGCGTG 540
AGGCGGGCGT GGTGCGGCTA CGCTTCGGCC TTACCGACGG CCAGCCGCGC ACCCTTGACG 600
AGATCGGCCA GGTCTACGGC GTGACCCGGG AACGCATCCG CCAGATCGAA TCCAAGACTA 660
TGTCGAAGTT GCGCCATCCG AGCCGCTCAC AGGTCCTGCG CGACTATCGT GCCGAATTCG 720
GCACGAGCCG TTTTGAGGTG CACGCCCAGA CGGTGGAGGA CGAGGCTCGC CGGATGTGGG 780
CGTCCGCGCA AAACATTTCC GGTGCGGGCT GGAGTGGCAT GGCCGANGCG ACCTCGCTAG 840
ACACCATGGC CCAGATGAAT CAGGCGTTTC GCAACATCGT GAACATGCTG CACGGGGTGC 900
GTGACGGGCT GGTTCGCGAC GCCAACAACT ACGAACAGCA AGAGCAGGCC TCCCAGCAGA 960
TCCTCAGCAG CTGACCCGGC CCGACGACTC AGGAGGACAC ATGACCATCA ACTATCAATT 1020
CGGGGACGTC GACGCTCATG GCGCCATGAT CCGCGCTCTG GCCGGGTTGC TGGAGGCCGA 1080
GCATCAGGCC ATCATTTCTG ATGTGTTGAC CGCGAGTGAC TTTTGGGGCG GCGCCGGTTC 1140
GGCGGCCTGC CAGGGGTTCA TTACCCAGTT GGGCCGTAAC TTCCAGGTGA TCTACGAGCA 1200
GGCCAACGCC CACGGGCAGA AGGTGCAGGC TGCCGGCAAC AACATGGCAC AAACCGACAG 1260
CGCCGTCGGC TCCAGCTGGG CCTAACCCGG GTCCTAAGTT GGGTCCGCGC AGGGCGGGCC 1320
GATCAGCGTC GACTTTGGCG CCCGATACAC GGGCATGTNG TNGTCGGGAA CACTGCGCCC 1380
GCGTCAGCTG CCCGCTTCCC CTTGTTCGGC GACGTGCTCG GTGATGGCTT TGACGACCGC 1440
TTCGCCGGCG CGGCCAATCA ATTGGTCGCG CTTGCCTCTA GCCTCGTGCC GAATTCGGCA 1500
CGAGGGTGCT GGTGCCGCGC TATCGGCAGC ACGTGAGCTC CACGACGAAC TCATCCCAGT 1560
GCTGGGTTCC GCGGAGTTCG GCATCGGCGT GTCGGCCGGA AGGGCCATCG CCGGCCACAT 1620
CGGCGCTCAA GCCCGCTTCG AGTACACCGT CATCGGCGAC CCGGTCAACG AGGCCGCCCG 1680
GCTCACCGAA CTGGCCAAAG TCGAGGATGG CCACGTTCTG GCGTCGGCGA TCGCGGTCAG 1740
TGGCGCCCTG GACGCCGAAG CATTGTGTTG GGATGTTGGC GAGGTGGTTG AGCTCCGCGG 1800
ACGTGCTGCA CCCACCCAAC TAGCCAGGCC AATGAATNTG GCNGCACCCG AAGAGGTTTC 1860
CAGCGAAGTA CGCGGCTAGT CGCGCTTGGC TGCNTTCTTC GCCGGCACCT TCCGGGCAGC 1920
TTTCCTGGCT GGCCGTTTTG CCGGACCCCG GGCTCGGCGA TCGGCCAACA GCTCGGCGGC 1980
GCGCTCGTCG GTTATGGAAG CCACGTNGTC GCCCTTACGC AGGCTGGCAT TGGTCTCACC 2040
GTCGGTGACG TACGGCCCGA ATCGGCCGTC CTTGATGACC ATTGGCTTGC CAGACGCCGG 2100
ATNTGNTCCC AGCTCGCGCA GCGGCGGAGC CGAAGCGCTT TGCCGGCCAC GACNTTTCGG 2160
CTCTGNGTAG ATNTTCAGGG CTTCGTCGAG CGNGATGGTG AATATATGGT CTTCGGTGAC 2220
CAGTGATCGA GAATCGTTGC CGCGCTTTAG ATACGGTCNG TAGCGCCCGT TCTGCGCGGT 2280
GATNTC 2286
(2) INFORMATION FOR SEQ ID NO:10:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 1136 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: DNA (genomic)
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:10:
GGGCATCTTC CCCGACCGCG CCTCGATCAT CCGCCTCGTC GGAGCCGTCC TCGCCGAACA 60
ACACGACGAA TGGATCGAAG GACGGCGCTA CCTGGGCCTC GAGGTCCTCA CCCGAGCCCG 120
AGCAGCACTG ACCAGCACCG AAGAACCGCC AAGCAGCAAA CCACCAACAC CCCAGCACTG 180
ACCACCTAGA CTGCCACCCG AAGGATCACG CGAGGAACCT TCACTCGTAC ACCACGTCCC 240
TGGCCTTGGC CTGGTGTCAG GCCCAGCTGG AGCCGACGGC GCTGTCGGTT TGCGCCATGT 300
TGTTGCCGGC AGCCTGCACC TTCTGCCCGT GGGCGTTGGC CTGCTCGTAG ATCACCTGGA 360
AGTTACGGCC CAACTGGGTA ATGAACCCCT GGCAGGCCGC CGAACCGGCG CCGCCCCAAA 420
AGTCACTCGC GGTCAACACA TCACGAATGA TGGCCTGATG CTCGGCCTCC AGCAACCCGG 480
CCTGAGCGCG GATCATGGCG CCGTGAGCGT CGACATCACC GAACTGATAG TTGATGGTCA 540
TCGAACCTGT TCTCCTTCGC TTGTAAAAGT ATTGTGCTGC AGCGGCTGAC GTTAGCTGCT 600
GAGGATCTGC TGGGAGGCCT GCTCTTGCCT CGTGCCGAAT TCGGCACGAG AGGCCGCCTT 660
CGAAGAAATC CTTTGAGAAT TCGCCAAGGC CGTCGACCCA GCATGGGGTC AGCTCGCCAG 720
CCGCGCCGGC TGGCAACCGT TCCCGCTCGA GAAAGACCTG GAGGAATACC AGTGACAAAC 780
GACCTCCCAG ACGTCCGAGA GCGTGACGGC GGTCCACGTC CCGCTCCTCC TGCTGGCGGG 840
CCACGCTTGT CAGACGTGTG GGTTTACAAC GGGCGGGCGT ACGACCTGAG TGAGTGGATT 900
TCCAAGCATC CCGGCGGCGC CTTNTTCATT GGGCGGACCA AGAACCGCGA CATCACCGCA 960
ATCGTCAAGT CCTACCATCG TGATCCGGCG ATTGTCGAGC GAATCCTGCA GCGGAGGTAC 1020
GCGTTGGGCC GCGACGCAAC CCCTAGGGAC ATCCACCCCA AGCACAATGC ACCGGCATTT 1080
CTGTTCAAAG ACGACTTCAA CAGCTGGCGG GACACCCCGA AGTATCGATT NGACGA 1136
(2) INFORMATION FOR SEQ ID NO:11:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 967 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: DNA (genomic)
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:11:
TGAGCGCCAA CCCTACCGTC GGTTCGTCAC ACGGACCGCA TGGCCTGCTC CGCGGACTGC 60
CGCTAGGGTC GCGGATCACT CGGCGTAGCG GCGCCTTTGC CCACCGATAT GGGTTCCGTC 120
ACAGTGTGGT TGCCCGCCCG CCATCGGCCG GATAACGCCA TGACCTCAGC TCGGCAGAAA 180
TGACAATGCT CCCAAAGGCG TGAGCACCCG AAGACAACTA AGCAGGAGAT CGCATGCCGT 240
TTGTGACTAC CCAACCAGAA GCACTGGCGG CGGCGGCCGG CAGTCTGCAG GGAATCGGCT 300
CCGCATTGAA CGCCCAGAAT GCGGCTGCGG CGACTCCCAC GACGGGGGTG GTCCGGCGGC 360
CGCCGATGAA NTGTCGGCGC TGACGGCGGC TCAGTTCGCG GCACACGCCC AGATCTATCA 420
GGCCGTCAGC GCCCAGGCCG CGGCGATTCA CGAGATGTTC GTCAACACTC TACAGATGAG 480
CTCAGGGTCG TATGCTGCTA CCGAGGCCGC CAACGCGGCC GCGGCCGGNT AGAGGAGTCA 540
CTGCGATGGA TTTTGGGGCG TTGCCGCCGG AGGTCAATTC GGTGCGGATG TATGCCGTTC 600
CTGGCTCGGC ACCAATGGTC GCTGCGGCGT CGGCCTGGAA CGGGTTGGCC GCGGAGCTGA 660
GTTCGGCGGC CACCGGTTAT GAGACGGTGA TCACTCAGCT CAGCAGTGAG GGGTGGCTAG 720
GTCCGGCGTC AGCGGCGATG GCCGAGGCAG TTGCGCCGTA TGTGGCGTGG ATGAGTGCCG 780
CTGCGGCGCA AGCCGAGCAG GCGGCCACAC AGGCCAGGGC CGCCGCGGCC GCTTTTGAGG 840
CGGCGTTTGC CGCGACGGTG CCTCCGCCGT TGATCGCGGC CAACCGGGCT TCGTTGATGC 900
AGCTGATCTC GACGAATGTC TTTGGTCAGA ACACCTCGGC GATCGCGGCC GCCGAAGCTC 960
AGTACGG 967
(2) INFORMATION FOR SEQ ID NO:12:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 585 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: DNA (genomic)
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:12:
TGGATTCCGA TAGCGGTTTC GGCCCCTCGA CGGGCGACCA CGGCGCGCAG GCCTCCGAAC 60
GGGGGGCCGG GACGCTGGGA TTCGCCGGGA CCGCAACCAA AGAACGCCGG GTCCGGGCGG 120
TCGGGCTGAC CGCACTGGCC GGTGATGAGT TCGGCAACGG CCCCCGGATG CCGATGGTGC 180
CGGGGACCTG GGAGCAGGGC AGCAACGAGC CCGAGGCGCC CGACGGATCG GGGAGAGGGG 240
GAGGCGACGG CTTACCGCAC GACAGCAAGT AACCGAATTC CGAATCACGT GGACCCGTAC 300
GGGTCGAAAG GAGAGATGTT ATGAGCCTTT TGGATGCTCA TATCCCACAG TTGGTGGCCT 360
CCCAGTCGGC GTTTGCCGCC AAGGCGGGGC TGATGCGGCA CACGATCGGT CAGGCCGAGC 420
AGGCGGCGAT GTCGGCTCAG GCGTTTCACC AGGGGGAGTC GTCGGCGGCG TTTCAGGCCG 480
CCCATGCCCG GTTTGTGGCG GCGGCCGCCA AAGTCAACAC CTTGTTGGAT GTCGCGCAGG 540
CGAATCTGGG TGAGGCCGCC GGTACCTATG TGGCCGCCGA TGCTG 585
(2) INFORMATION FOR SEQ ID NO:13:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 144 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:13:
Ala Leu Val Thr Thr Asn Phe Phe Gly Val Asn Thr Ile Pro Ile Ala
1 5 10 15
Leu Asn Glu Ala Asp Tyr Leu Arg Met Trp Ile Gln Ala Ala Thr Val
20 25 30
Met Ser His Tyr Gln Ala Val Ala His Glu Ile Trp Cys Leu His Glu
35 40 45
Xaa Ala Ser Ser Gly Lys Pro Trp Ala Ser Ile Thr Thr Gly Ala Pro
50 55 60
Gly Ser Pro Ala Ser Thr Thr Arg Ser Arg Thr Pro Leu Val Ser Thr
65 70 75 80
Asn Arg Xaa Val Xaa Ala Pro Ile Val Ser Pro Asn His Thr Gly His
85 90 95
Arg Pro Glu Lys Gly Leu Gly Ser Xaa Gln Arg Arg Leu Ser Arg Val
100 105 110
Leu Pro Arg Ile Ile Asp Arg Pro Ala Gly Pro Xaa Gly Pro Pro Leu
115 120 125
Thr Ser Gly Ser His Phe Leu Cys Ser Trp His Gly Tyr Ser Ser Gln
130 135 140
(2) INFORMATION FOR SEQ ID NO:14:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 352 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:14:
His Ala Leu Ala Ala Gln Tyr Thr Glu Ile Ala Thr Glu Leu Ala Ser
1 5 10 15
Val Leu Ala Ala Val Gln Ala Ser Ser Trp Gln Gly Pro Ser Ala Asp
20 25 30
Arg Phe Val Val Ala His Gln Pro Phe Arg Tyr Trp Leu Thr His Ala
35 40 45
Ala Thr Val Ala Thr Ala Ala Ala Ala Ala His Xaa Thr Ala Ala Ala
50 55 60
Gly Tyr Thr Ser Ala Leu Gly Gly Met Pro Thr Leu Ala Glu Leu Ala
65 70 75 80
Ala Asn His Ala Met His Gly Ala Leu Val Thr Thr Asn Phe Phe Gly
85 90 95
Val Asn Thr Ile Pro Ile Ala Leu Asn Glu Ala Asp Tyr Leu Arg Met
100 105 110
Trp Ile Gln Ala Ala Thr Val Met Ser His Tyr Gln Ala Val Ala His
115 120 125
Glu Ser Val Ala Ala Thr Pro Ser Thr Pro Pro Ala Pro Gln Ile Val
130 135 140
Thr Ser Ala Ala Ser Ser Ala Ala Ser Ser Ser Phe Pro Asp Pro Thr
145 150 155 160
Lys Leu Ile Leu Gln Leu Leu Lys Asp Phe Leu Glu Leu Leu Arg Tyr
165 170 175
Leu Ala Val Glu Leu Leu Pro Gly Pro Leu Gly Asp Leu Ile Ala Gln
180 185 190
Val Leu Asp Trp Phe Ile Ser Phe Val Ser Gly Pro Val Phe Thr Phe
195 200 205
Leu Ala Tyr Leu Val Leu Asp Pro Leu Ile Tyr Phe Gly Pro Phe Ala
210 215 220
Pro Leu Thr Ser Pro Val Leu Leu Pro Ala Val Glu Leu Arg Asn Arg
225 230 235 240
Leu Lys Thr Ala Thr Gly Leu Thr Leu Pro Pro Thr Val Ile Phe Asp
245 250 255
His Pro Thr Pro Thr Ala Val Ala Glu Tyr Val Ala Gln Gln Met Ser
260 265 270
Gly Ser Arg Pro Thr Glu Ser Gly Asp Pro Thr Ser Gln Val Val Glu
275 280 285
Pro Ala Arg Ala Glu Phe Gly Thr Ser Ala Val His Gln Ile Pro Pro
290 295 300
Arg Pro Ala Asp Thr Arg Arg Ala Cys Arg His Arg Asp Asp Val Pro
305 310 315 320
Arg Asp Ser Arg Ile Ala Gln His Arg Asp Gly Ala Gly Leu Asp Pro
325 330 335
Thr Glu Arg Gly Thr Ser Glu Gly Asp Gln Gly Leu Val Ser Gly Trp
340 345 350
(2) INFORMATION FOR SEQ ID NO:15:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 141 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:15:
Met Asp Phe Gly Ala Leu Pro Pro Glu Val Asn Ser Val Arg Met Tyr
1 5 10 15
Ala Val Pro Gly Ser Ala Pro Met Val Ala Ala Ala Ser Ala Trp Asn
20 25 30
Gly Leu Ala Ala Glu Leu Ser Ser Ala Ala Thr Gly Tyr Glu Thr Val
35 40 45
Ile Thr Gln Leu Ser Ser Glu Gly Trp Leu Gly Pro Ala Ser Ala Ala
50 55 60
Met Ala Glu Ala Val Ala Pro Tyr Val Ala Trp Met Ser Ala Ala Ala
65 70 75 80
Ala Gln Ala Glu Gln Ala Ala Thr Gln Ala Arg Ala Ala Ala Ala Ala
85 90 95
Phe Glu Ala Ala Phe Ala Ala Thr Val Pro Pro Pro Leu Ile Ala Ala
100 105 110
Asn Arg Ala Ser Leu Met Gln Leu Ile Ser Thr Asn Val Phe Gly Gln
115 120 125
Asn Thr Ser Ala Ile Ala Ala Ala Glu Ala Gln Tyr Gly
130 135 140
(2) INFORMATION FOR SEQ ID NO:16:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 58 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:16:
Met Ala Ser Arg Phe Met Thr Asp Pro His Ala Met Arg Asp Met Ala
1 5 10 15
Gly Arg Phe Glu Val His Ala Gln Thr Val Glu Asp Glu Ala Arg Arg
20 25 30
Met Trp Ala Ser Ala Gln Asn Ile Ser Gly Ala Gly Trp Ser Gly Met
35 40 45
Ala Glu Ala Thr Ser Leu Asp Thr Met Thr
50 55
(2) INFORMATION FOR SEQ ID NO:17:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 67 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:17:
Met Thr Ile Asn Tyr Gln Phe Gly Asp Val Asp Ala His Gly Ala Met
1 5 10 15
Ile Arg Ala Gln Ala Ala Ser Leu Glu Ala Glu His Gln Ala Ile Val
20 25 30
Arg Asp Val Leu Ala Ala Gly Asp Phe Trp Gly Gly Ala Gly Ser Val
35 40 45
Ala Cys Gln Glu Phe Ile Thr Gln Leu Gly Arg Asn Phe Gln Val Ile
50 55 60
Tyr Glu Gln
65
(2) INFORMATION FOR SEQ ID NO:18:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 58 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:18:
Met Ala Ser Arg Phe Met Thr Asp Pro His Ala Met Arg Asp Met Ala
1 5 10 15
Gly Arg Phe Glu Val His Ala Gln Thr Val Glu Asp Glu Ala Arg Arg
20 25 30
Met Trp Ala Ser Ala Gln Asn Ile Ser Gly Ala Gly Trp Ser Gly Met
35 40 45
Ala Glu Ala Thr Ser Leu Asp Thr Met Thr
50 55
(2) INFORMATION FOR SEQ ID NO:19:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 94 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:19:
Met Thr Ile Asn Tyr Gln Phe Gly Asp Val Asp Ala His Gly Ala Met
1 5 10 15
Ile Arg Ala Gln Ala Ala Ser Leu Glu Ala Glu His Gln Ala Ile Val
20 25 30
Arg Asp Val Leu Ala Ala Gly Asp Phe Trp Gly Gly Ala Gly Ser Val
35 40 45
Ala Cys Gln Glu Phe Ile Thr Gln Leu Gly Arg Asn Phe Gln Val Ile
50 55 60
Tyr Glu Gln Ala Asn Ala His Gly Gln Lys Val Gln Ala Ala Gly Asn
65 70 75 80
Asn Met Ala Gln Thr Asp Ser Ala Val Gly Ser Ser Trp Ala
85 90
(2) INFORMATION FOR SEQ ID NO:20:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 30 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:20:
Asn Met Leu His Gly Val Arg Asp Gly Leu Val Arg Asp Ala Asn Asn
1 5 10 15
Tyr Glu Gln Gln Glu Gln Ala Ser Gln Gln Ile Leu Ser Ser
20 25 30
(2) INFORMATION FOR SEQ ID NO:21:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 94 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:21:
Met Thr Ile Asn Tyr Gln Phe Gly Asp Val Asp Ala His Gly Ala Met
1 5 10 15
Ile Arg Ala Gln Ala Gly Leu Leu Glu Ala Glu His Gln Ala Ile Ile
20 25 30
Arg Asp Val Leu Thr Ala Ser Asp Phe Trp Gly Gly Ala Gly Ser Ala
35 40 45
Ala Cys Gln Gly Phe Ile Thr Gln Leu Gly Arg Asn Phe Gln Val Ile
50 55 60
Tyr Glu Gln Ala Asn Ala His Gly Gln Lys Val Gln Ala Ala Gly Asn
65 70 75 80
Asn Met Ala Gln Thr Asp Ser Ala Val Gly Ser Ser Trp Ala
85 90
(2) INFORMATION FOR SEQ ID NO:22:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 69 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:22:
Ala Arg Arg Met Trp Ala Ser Ala Gln Asn Ile Ser Gly Ala Gly Trp
1 5 10 15
Ser Gly Met Ala Glu Ala Thr Ser Leu Asp Thr Met Ala Gln Met Asn
20 25 30
Gln Ala Phe Arg Asn Ile Val Asn Met Leu His Gly Val Arg Asp Gly
35 40 45
Leu Val Arg Asp Ala Asn Asn Tyr Glu Gln Gln Glu Gln Ala Ser Gln
50 55 60
Gln Ile Leu Ser Ser
65
(2) INFORMATION FOR SEQ ID NO:23:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 94 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:23:
Met Thr Ile Asn Tyr Gln Phe Gly Asp Val Asp Ala His Gly Ala Met
1 5 10 15
Ile Arg Ala Gln Ala Gly Leu Leu Glu Ala Glu His Gln Ala Ile Ile
20 25 30
Arg Asp Val Leu Thr Ala Ser Asp Phe Trp Gly Gly Ala Gly Ser Ala
35 40 45
Ala Cys Gln Gly Phe Ile Thr Gln Leu Gly Arg Asn Phe Gln Val Ile
50 55 60
Tyr Glu Gln Ala Asn Thr His Gly Gln Lys Val Gln Ala Ala Gly Asn
65 70 75 80
Asn Met Ala Gln Thr Asp Ser Ala Val Xaa Ser Ser Trp Ala
85 90
(2) INFORMATION FOR SEQ ID NO:24:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 52 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:24:
Gly Met Ala Glu Ala Thr Ser Xaa Asp Thr Met Thr Gln Met Asn Gln
1 5 10 15
Ala Phe Arg Asn Ile Val Asn Met Leu His Gly Val Arg Asp Gly Leu
20 25 30
Val Arg Asp Ala Asn Xaa Tyr Glu Gln Gln Glu Gln Ala Ser Gln Gln
35 40 45
Ile Leu Ser Ser
50
(2) INFORMATION FOR SEQ ID NO:25:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 94 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:25:
Met Thr Ile Asn Tyr Gln Phe Gly Asp Val Asp Ala His Gly Ala Met
1 5 10 15
Ile Arg Ala Gln Ala Gly Ser Leu Glu Ala Glu His Gln Ala Ile Ile
20 25 30
Ser Asp Val Leu Thr Ala Ser Asp Phe Trp Gly Gly Ala Gly Ser Ala
35 40 45
Ala Cys Gln Gly Phe Ile Thr Gln Leu Gly Arg Asn Phe Gln Val Xaa
50 55 60
Tyr Glu Gln Ala Asn Ala His Gly Gln Lys Val Gln Ala Ala Gly Asn
65 70 75 80
Asn Met Ala Gln Thr Asp Ser Ala Val Gly Ser Ser Trp Ala
85 90
(2) INFORMATION FOR SEQ ID NO:26:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 98 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:26:
Met Thr Ser Arg Phe Met Thr Asp Pro His Ala Met Arg Asp Met Ala
1 5 10 15
Gly Arg Phe Glu Val His Ala Gln Thr Val Glu Asp Glu Ala Arg Arg
20 25 30
Met Trp Ala Ser Ala Gln Asn Ile Ser Gly Ala Gly Trp Ser Gly Met
35 40 45
Ala Glu Ala Thr Ser Leu Asp Thr Met Ala Gln Met Asn Gln Ala Phe
50 55 60
Arg Asn Ile Val Asn Met Leu His Gly Val Arg Asp Gly Leu Val Arg
65 70 75 80
Asp Ala Asn Asn Tyr Glu Gln Gln Glu Gln Ala Ser Gln Gln Ile Leu
85 90 95
Ser Ser
(2) INFORMATION FOR SEQ ID NO:27:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 94 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:27:
Met Thr Ile Asn Tyr Gln Phe Gly Asp Val Asp Ala His Gly Ala Met
1 5 10 15
Ile Arg Ala Xaa Ala Gly Leu Leu Glu Ala Glu His Gln Ala Ile Ile
20 25 30
Ser Asp Val Leu Thr Ala Ser Asp Phe Trp Gly Gly Ala Gly Ser Ala
35 40 45
Ala Cys Gln Gly Phe Ile Thr Gln Leu Gly Arg Asn Phe Gln Val Ile
50 55 60
Tyr Glu Gln Ala Asn Ala His Gly Gln Lys Val Gln Ala Ala Gly Asn
65 70 75 80
Asn Met Ala Gln Thr Asp Ser Ala Val Gly Ser Ser Trp Ala
85 90
(2) INFORMATION FOR SEQ ID NO:28:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 81 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:28:
Arg Phe Glu Val His Ala Gln Thr Val Glu Asp Glu Ala Arg Arg Met
1 5 10 15
Trp Ala Ser Ala Gln Asn Ile Ser Gly Ala Gly Trp Ser Gly Met Ala
20 25 30
Xaa Ala Thr Ser Leu Asp Thr Met Ala Gln Met Asn Gln Ala Phe Arg
35 40 45
Asn Ile Val Asn Met Leu His Gly Val Arg Asp Gly Leu Val Arg Asp
50 55 60
Ala Asn Asn Tyr Glu Gln Gln Glu Gln Ala Ser Gln Gln Ile Leu Ser
65 70 75 80
Ser
(2) INFORMATION FOR SEQ ID NO:29:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 94 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:29:
Met Thr Ile Asn Tyr Gln Phe Gly Asp Val Asp Ala His Gly Ala Met
1 5 10 15
Ile Arg Ala Leu Ala Gly Leu Leu Glu Ala Glu His Gln Ala Ile Ile
20 25 30
Ser Asp Val Leu Thr Ala Ser Asp Phe Trp Gly Gly Ala Gly Ser Ala
35 40 45
Ala Cys Gln Gly Phe Ile Thr Gln Leu Gly Arg Asn Phe Gln Val Ile
50 55 60
Tyr Glu Gln Ala Asn Ala His Gly Gln Lys Val Gln Ala Ala Gly Asn
65 70 75 80
Asn Met Ala Gln Thr Asp Ser Ala Val Gly Ser Ser Trp Ala
85 90
(2) INFORMATION FOR SEQ ID NO:30:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 11 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:30:
Gln Glu Gln Ala Ser Gln Gln Ile Leu Ser Ser
1 5 10
(2) INFORMATION FOR SEQ ID NO:31:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 94 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:31:
Met Thr Ile Asn Tyr Gln Phe Gly Asp Val Asp Ala His Gly Ala Met
1 5 10 15
Ile Arg Ala Gln Ala Gly Leu Leu Glu Ala Glu His Gln Ala Ile Ile
20 25 30
Arg Asp Val Leu Thr Ala Ser Asp Phe Trp Gly Gly Ala Gly Ser Ala
35 40 45
Ala Cys Gln Gly Phe Ile Thr Gln Leu Gly Arg Asn Phe Gln Val Ile
50 55 60
Tyr Glu Gln Ala Asn Ala His Gly Gln Lys Val Gln Ala Ala Gly Asn
65 70 75 80
Asn Met Ala Gln Thr Asp Ser Ala Val Gly Ser Ser Trp Ala
85 90
(2) INFORMATION FOR SEQ ID NO:32:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 99 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:32:
Met Ser Phe Val Thr Thr Gln Pro Glu Ala Leu Ala Ala Ala Ala Ala
1 5 10 15
Asn Leu Gln Gly Ile Gly Thr Thr Met Asn Ala Gln Asn Ala Ala Ala
20 25 30
Ala Ala Pro Thr Thr Gly Val Val Pro Ala Ala Ala Asp Glu Val Ser
35 40 45
Ala Leu Thr Ala Ala Gln Phe Ala Ala His Ala Gln Met Tyr Gln Thr
50 55 60
Val Ser Ala Gln Ala Ala Ala Ile His Glu Met Phe Val Asn Thr Leu
65 70 75 80
Val Ala Ser Ser Gly Ser Tyr Ala Ala Thr Glu Ala Ala Asn Ala Ala
85 90 95
Ala Ala Gly
(2) INFORMATION FOR SEQ ID NO:33:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 99 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:33:
Met Ser Phe Val Thr Thr Gln Pro Glu Ala Leu Ala Ala Ala Ala Ala
1 5 10 15
Asn Leu Gln Gly Ile Gly Thr Thr Met Asn Ala Gln Asn Ala Ala Ala
20 25 30
Ala Ala Pro Thr Thr Gly Val Val Pro Ala Ala Ala Asp Glu Val Ser
35 40 45
Ala Leu Thr Ala Ala Gln Phe Ala Ala His Ala Gln Met Tyr Gln Thr
50 55 60
Val Ser Ala Gln Ala Ala Ala Ile His Glu Met Phe Val Asn Thr Leu
65 70 75 80
Val Ala Ser Ser Gly Ser Tyr Ala Ala Thr Glu Ala Ala Asn Ala Ala
85 90 95
Ala Ala Gly
(2) INFORMATION FOR SEQ ID NO:34:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:34:
Asp Pro His Ala Met Arg Asp Met Ala Gly Arg Phe Glu Val His
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:35:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:35:
Arg Asp Met Ala Gly Arg Phe Glu Val His Ala Gln Thr Val Glu
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:36:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:36:
Arg Phe Glu Val His Ala Gln Thr Val Glu Asp Glu Ala Arg Arg
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:37:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:37:
Ala Gln Thr Val Glu Asp Glu Ala Arg Arg Met Trp Ala Ser Ala
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:38:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:38:
Asp Glu Ala Arg Arg Met Trp Ala Ser Ala Gln Asn Ile Ser Gly
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:39:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:39:
Met Trp Ala Ser Ala Gln Asn Ile Ser Gly Ala Gly Trp Ser Gly
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:40:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:40:
Gln Asn Ile Ser Gly Ala Gly Trp Ser Gly Met Ala Glu Ala Thr
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:41:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 16 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:41:
Ala Gly Trp Ser Gly Met Ala Glu Ala Thr Ser Leu Asp Thr Met Thr
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:42:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:42:
Met Ala Glu Ala Thr Ser Leu Asp Thr Met Ala Gln Met Asn Gln
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:43:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:43:
Ser Leu Asp Thr Met Ala Gln Met Asn Gln Ala Phe Arg Asn Ile
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:44:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:44:
Ala Gln Met Asn Gln Ala Phe Arg Asn Ile Val Asn Met Leu His
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:45:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:45:
Ala Phe Arg Asn Ile Val Asn Met Leu His Gly Val Arg Asp Gly
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:46:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:46:
Val Asn Met Leu His Gly Val Arg Asp Gly Leu Val Arg Asp Ala
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:47:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:47:
Gly Val Arg Asp Gly Leu Val Arg Asp Ala Asn Asn Tyr Glu Gln
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:48:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:48:
Leu Val Arg Asp Ala Asn Asn Tyr Glu Gln Gln Glu Gln Ala Ser
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:49:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 16 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:49:
Asn Asn Tyr Glu Gln Gln Glu Gln Ala Ser Gln Gln Ile Leu Ser Ser
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:50:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 17 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:50:
Met Ala Ser Arg Phe Met Thr Asp Pro His Ala Met Arg Asp Met Ala
1 5 10 15
Gly
(2) INFORMATION FOR SEQ ID NO:51:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:51:
Met Thr Ile Asn Tyr Gln Phe Gly Asp Val Asp Ala His Gly Ala
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:52:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:52:
Gln Phe Gly Asp Val Asp Ala His Gly Ala Met Ile Arg Ala Gln
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:53:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:53:
Asp Ala His Gly Ala Met Ile Arg Ala Gln Ala Ala Ser Leu Glu
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:54:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:54:
Met Ile Arg Ala Gln Ala Ala Ser Leu Glu Ala Glu His Gln Ala
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:55:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:55:
Ala Ala Ser Leu Glu Ala Glu His Gln Ala Ile Val Arg Asp Val
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:56:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:56:
Ala Glu His Gln Ala Ile Val Arg Asp Val Leu Ala Ala Gly Asp
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:57:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:57:
Ile Val Arg Asp Val Leu Ala Ala Gly Asp Phe Trp Gly Gly Ala
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:58:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 16 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:58:
Leu Ala Ala Gly Asp Phe Trp Gly Gly Ala Gly Ser Val Ala Cys Gln
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:59:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:59:
Phe Trp Gly Gly Ala Gly Ser Val Ala Cys Gln Glu Phe Ile Thr
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:60:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:60:
Gly Ser Val Ala Cys Gln Glu Phe Ile Thr Gln Leu Gly Arg Asn
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:61:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 18 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:61:
Gln Glu Phe Ile Thr Gln Leu Gly Arg Asn Phe Gln Val Ile Tyr Glu
1 5 10 15
Gln Ala
(2) INFORMATION FOR SEQ ID NO:62:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:62:
Arg Asn Phe Gln Val Ile Tyr Glu Gln Ala Asn Ala His Gly Gln
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:63:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:63:
Ile Tyr Glu Gln Ala Asn Ala His Gly Gln Lys Val Gln Ala Ala
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:64:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:64:
Asn Ala His Gly Gln Lys Val Gln Ala Ala Gly Asn Asn Met Ala
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:65:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:65:
Lys Val Gln Ala Ala Gly Asn Asn Met Ala Gln Thr Asp Ser Ala
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:66:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 16 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:66:
Gly Asn Asn Met Ala Gln Thr Asp Ser Ala Val Gly Ser Ser Trp Ala
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:67:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:67:
Asp Ala His Gly Ala Met Ile Arg Ala Leu Ala Gly Leu Leu Glu
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:68:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:68:
Asp Ala His Gly Ala Met Ile Arg Ala Gln Ala Gly Leu Leu Glu
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:69:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:69:
Met Ile Arg Ala Leu Ala Gly Leu Leu Glu Ala Glu His Gln Ala
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:70:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:70:
Met Ile Arg Ala Gln Ala Gly Leu Leu Glu Ala Glu His Gln Ala
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:71:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:71:
Ala Gly Leu Leu Glu Ala Glu His Gln Ala Ile Ile Ser Asp Val
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:72:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:72:
Ala Gly Leu Leu Glu Ala Glu His Gln Ala Ile Ile Arg Asp Val
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:73:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:73:
Ala Glu His Gln Ala Ile Ile Ser Asp Val Leu Thr Ala Ser Asp
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:74:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:74:
Ala Glu His Gln Ala Ile Ile Arg Asp Val Leu Thr Ala Ser Asp
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:75:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:75:
Ile Ile Ser Asp Val Leu Thr Ala Ser Asp Phe Trp Gly Gly Ala
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:76:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:76:
Ile Ile Arg Asp Val Leu Thr Ala Ser Asp Phe Trp Gly Gly Ala
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:77:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 16 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:77:
Leu Thr Ala Ser Asp Phe Trp Gly Gly Ala Gly Ser Ala Ala Cys Gln
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:78:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:78:
Phe Trp Gly Gly Ala Gly Ser Ala Ala Cys Gln Gly Phe Ile Thr
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:79:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:79:
Gly Ser Ala Ala Cys Gln Gly Phe Ile Thr Gln Leu Gly Arg Asn
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:80:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:80:
Gln Gly Phe Ile Thr Gln Leu Gly Arg Asn Phe Gln Val Ile Tyr
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:81:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 25 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:81:
Val Thr Thr Asn Phe Phe Gly Val Asn Thr Ile Pro Ile Ala Leu Asn
1 5 10 15
Glu Ala Asp Tyr Leu Arg Met Trp Ile
20 25
(2) INFORMATION FOR SEQ ID NO:82:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 25 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:82:
Asn Glu Ala Asp Tyr Leu Arg Met Trp Ile Gln Ala Ala Thr Val Met
1 5 10 15
Ser His Tyr Gln Ala Val Ala His Glu
20 25
(2) INFORMATION FOR SEQ ID NO:83:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 967 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: cDNA
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:83:
TGAGCGCCAA CCCTACCGTC GGTTCGTCAC ACGGACCGCA TGGCCTGCTC CGCGGACTGC 60
CGCTAGGGTC GCGGATCACT CGGCGTAGCG GCGCCTTTGC CCACCGATAT GGGTTCCGTC 120
ACAGTGTGGT TGCCCGCCCG CCATCGGCCG GATAACGCCA TGACCTCAGC TCGGCAGAAA 180
TGACAATGCT CCCAAAGGCG TGAGCACCCG AAGACAACTA AGCAGGAGAT CGCATGCCGT 240
TTGTGACTAC CCAACCAGAA GCACTGGCGG CGGCGGCCGG CAGTCTGCAG GGAATCGGCT 300
CCGCATTGAA CGCCCAGAAT GCGGCTGCGG CGACTCCCAC GACGGGGGTG GTCCGGCGGC 360
CGCCGATGAA NTGTCGGCGC TGACGGCGGC TCAGTTCGCG GCACACGCCC AGATCTATCA 420
GGCCGTCAGC GCCCAGGCCG CGGCGATTCA CGAGATGTTC GTCAACACTC TACAGATGAG 480
CTCAGGGTCG TATGCTGCTA CCGAGGCCGC CAACGCGGCC GCGGCCGGNT AGAGGAGTCA 540
CTGCGATGGA TTTTGGGGCG TTGCCGCCGG AGGTCAATTC GGTGCGGATG TATGCCGTTC 600
CTGGCTCGGC ACCAATGGTC GCTGCGGCGT CGGCCTGGAA CGGGTTGGCC GCGGAGCTGA 660
GTTCGGCGGC CACCGGTTAT GAGACGGTGA TCACTCAGCT CAGCAGTGAG GGGTGGCTAG 720
GTCCGGCGTC AGCGGCGATG GCCGAGGCAG TTGCGCCGTA TGTGGCGTGG ATGAGTGCCG 780
CTGCGGCGCA AGCCGAGCAG GCGGCCACAC AGGCCAGGGC CGCCGCGGCC GCTTTTGAGG 840
CGGCGTTTGC CGCGACGGTG CCTCCGCCGT TGATCGCGGC CAACCGGGCT TCGTTGATGC 900
AGCTGATCTC GACGAATGTC TTTGGTCAGA ACACCTCGGC GATCGCGGCC GCCGAAGCTC 960
AGTACGG 967
(2) INFORMATION FOR SEQ ID NO:84:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:84:
Met Ser Phe Val Thr Thr Gln Pro Glu Ala Leu Ala Ala Ala Ala
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:85:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:85:
Thr Gln Pro Glu Ala Leu Ala Ala Ala Ala Ala Asn Leu Gln Gly
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:86:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:86:
Leu Ala Ala Ala Ala Ala Asn Leu Gln Gly Ile Gly Thr Thr Met
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:87:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:87:
Ala Asn Leu Gln Gly Ile Gly Thr Thr Met Asn Ala Gln Asn Ala
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:88:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:88:
Ile Gly Thr Thr Met Asn Ala Gln Asn Ala Ala Ala Ala Ala Pro
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:89:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:89:
Asn Ala Gln Asn Ala Ala Ala Ala Ala Pro Thr Thr Gly Val Val
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:90:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:90:
Ala Ala Ala Ala Pro Thr Thr Gly Val Val Pro Ala Ala Ala Asp
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:91:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:91:
Thr Thr Gly Val Val Pro Ala Ala Ala Asp Glu Val Ser Ala Leu
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:92:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:92:
Pro Ala Ala Ala Asp Glu Val Ser Ala Leu Thr Ala Ala Gln Phe
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:93:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:93:
Glu Val Ser Ala Leu Thr Ala Ala Gln Phe Ala Ala His Ala Gln
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:94:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:94:
Thr Ala Ala Gln Phe Ala Ala His Ala Gln Met Tyr Gln Thr Val
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:95:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:95:
Ala Ala His Ala Gln Met Tyr Gln Thr Val Ser Ala Gln Ala Ala
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:96:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 16 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:96:
Met Tyr Gln Thr Val Ser Ala Gln Ala Ala Ala Ile His Glu Met Phe
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:97:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:97:
Ser Ala Gln Ala Ala Ala Ile His Glu Met Phe Val Asn Thr Leu
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:98:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:98:
Ala Ile His Glu Met Phe Val Asn Thr Leu Val Ala Ser Ser Gly
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:99:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:99:
Phe Val Asn Thr Leu Val Ala Ser Ser Gly Ser Tyr Ala Ala Thr
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:100:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:100:
Val Ala Ser Ser Gly Ser Tyr Ala Ala Thr Glu Ala Ala Asn Ala
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:101:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 14 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:101:
Ser Tyr Ala Ala Thr Glu Ala Ala Asn Ala Ala Ala Ala Gly
1 5 10
(2) INFORMATION FOR SEQ ID NO:102:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 1784 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: cDNA
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:102:
ATTCGTTCCT GCCGCAGCTA AATCCCGGGG ACATCGTCGC CGGCCAGTAC GAGGTCAAAG 60
GCTGCATCGC GCACGGCGGA CTGGGCTGGA TCTACCTCGC TCTCGACCGC AATGTCAACG 120
GCCGTCCGGT GGTGCTCAAG GGCCTGGTGC ATTCCGGTGA TGCCGAAGCG CAGGCAATGG 180
CGATGGCCGA ACGCCAGTTC CTGGCCGAGG TGGTGCACCC GTCGATCGTG CAGATCTTCA 240
ACTTTGTCGA GCACACCGAC AGGCACGGGG ATCCGGTCGG CTACATCGTG ATGGAATACG 300
TCGGCGGGCA ATCGCTCAAA CGCAGCAAGG GTCANAAACT GCCCGTCGCG GAGGCCATCG 360
CCTACCTGCT GGAGATCCTG CCGGCGCTGA GCTACCTGCA TTCCATCGGC TTGGTCTACA 420
ACGACCTGAA GCCGGAAAAC ATCATGCTGA CCGAGGAACA GCTCAAGCTG ATCGACCTGG 480
GCGCGGTATC GCGGATCAAC TCGTTCGGCT ACCTCTACGG GACCCCAGGC TTCCAGGCGC 540
CCGAGATCGT GCGGACCGGT CCGACGGTGG CCACCGACAT CTACACCGTG GGACGCACGC 600
TCGCGGCGCT CACGCTGGAC CTGCCCACCC GCAATGGCCG TTATGTGGAT GGGCTACCCG 660
AAGACGACCC GGTGCTGAAA ACCTACGACT CTTACGGCCG GTTGCTGCGC AGGGCCATCG 720
ACCCCGATCC GCGGCAACGG TTCACCACCG CCGAAGAGAT GTCCGCGCAA TTGACGGGCG 780
TGTTGCGGGA GGTGGTCGCC CAGACACCGG GGTGCCGCGG CCAGGCTATC AACGATCTTC 840
AGTCCCAGTC GGTCGACATT TGGAGTGGAC TGCTGGTGGC GCACACCGAC GTGTATCTGG 900
ACGGGCAGGT GCACGCGGAG AAGCTGACCG CCAACGAGAT CGTGACCGCG CTGTCGGTGC 960
CGCTGGTCGA TCCGACCGAC GTCGCAGCTT CGGTCCTGCA GGCCACGGTG CTCTCCCAGC 1020
CGGTGCAGAC CCTAGACTCG NTGCGCGCGG CCCGCCACGG TGCGCTGGAC GCCGACGGCG 1080
TCGATTNTCC GAGTCAGTGG AGCTGCCGCT AATGGAAGTC CGCGCGCTGC TGGATCTCGG 1140
CGATGTGGCC AAGGCCACCC GAAAACTCGA CGATCTGGCC GAACGCGTTG GCTGGCGATG 1200
GCGATTGGTC TGGTACCGGG CCGTCGCCGA GCTGCTCACC GGCGACTATG ACTCGGCCAC 1260
CAAACATTTC ACCGAGGTGC TGGATACCTT TCCCGGCGAG CTGGCGCCCA AGCTCGCCCT 1320
GGCCGCCACC GCCGAACTAG CCGGCAACAC CGACGAACAC AAGTTCTATC AGACGGTGTG 1380
GAGCACCAAC GACGGCGTGA TCTCGGCGGC TTTCGGACTG GCCAGAGCCC GGTCGGCCGA 1440
AGGTGATCGG GTCGGCGCCG TGCGCACGCT CGACGAGGTA CCGCCCACTT CTCGGCATTT 1500
CACCACGGCA CGGCTGACCA GCGCGGTGAC TCTGTTGTCC GGCCGGTCAA CGAGTGAAGT 1560
CACCGAGGAA CAGATCCGCG ACGCCGCCCG AAGAGTGGAG GCGCTGCCCC CGACCGAACC 1620
ACGCGTGCTG CAGATCCGCG CCCTGGTGCT GGGTGGCGCG CTGGACTGGC TGAAGGACAA 1680
CAAGGCCAGC ACCAACCACA TCCTCGGTTT CCCGTTCACC AGTCACGGGC TGCGGCTGGG 1740
TGTCGAGGCG TCACTGCGCA GCCTGGCCCG GGTAGCTCCC ACTC 1784
(2) INFORMATION FOR SEQ ID NO:103:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 766 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: cDNA
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:103:
ACAARACACT CGGYGGCKGC CGMTCCGGCC TGATCGTCGG TGATCAGCYT CGTGCCAAAY 60
TCGGCACAAG GTGCGCGCTR CCCAANGAGT TCTTCGCCGC RGTGCGMGCM KAACTGGCCT 120
ATCNTGGTTG GGTGCCGTCC CGCANAACCC GCGAACTTAA ACCCATTTTA ACCGGGCAGG 180
AAGTTTCCTA CATYTACCCN RGSMANCCAA CCGGGCCGCC NANAAMTCCG TCCTGGANTC 240
CGANCGGTTC CCGGTGTTCG CCGCACTGCT GACCGGCACG GARTATCCGC AGGCGGCGTT 300
GGCCAACGCG TGGGTGCAAC TGGCCTACGG TGCGCACCAS GACGCCATCA CCGGCTCGGA 360
GTCCGACCAG GTACTCAATG CTGGCGACCA CACCAGCCAG CAGACCAAAC TGGTGCACGC 420
CGATCTCCAG GCGCGCCGGC CCGGTGGCAT ACGGATTGGT CGAAACCAAT CCGAAGGAAT 480
TCATCACGGA CGGTCACGGA AAACGATCGC CCCAATGGGN GGACNACCCN AGCCAGGCGN 540
ATTNACCGTT NAACAAGTTG GNGTAGGTTC TTTGATATCG AKCAACCGAT ACGGAKCGGM 600
CCGCGGAATG GTAGACCACC ACCAGTGCCC NCAMGTMGTG CACCAGTTTG GTCATCGCCC 660
GCAGATCGGT GACCCCGCCA AGCGTTCCGG ATGCGGAGAT GASGGTGACC AGCCYGGTTG 720
ACCTGTTGAT CAGGTTNTCC CAGTGCCACG TCGGCAGCTG GCCGGT 766
(2) INFORMATION FOR SEQ ID NO:104:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 1231 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: cDNA
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:104:
CGGCACGAGA ATGTCGCCTG TGCCTCGATA GCCACTTGCG TGTGGTCGCG CTGCCAGCGG 60
GTCAGCCAGG TCGCCTGGTC CAGGCCATCG GGCCGGCGCA GGAGCGCGAT GTTGGCCAGA 120
CCCGGTGTAC GAGAACCGGA CTCGACNAAG TGTCGGCGCT GACGGCGGCT CAGTTCGCGG 180
CACACGCCCA GATCTATCAG GCCGTCAGCG CCCAGGCCGC GGCGATTCAC GAGATGTTCG 240
TCAACACTCT ACAGATNANC TCAGGGTCGT ATGCTGCTAC CGAGGCCGCC AACGCGGCCG 300
CGGCCGGCTA GAGGAGTCAC TGCGATGGAT TTTGGGGCGT TGCCGCCGGA GGTCAATTCG 360
GTGCGGATGT ATGCCGGTCC TGGCTCGGCA CCAATGGTCG CTGCGGCGTC GGCCTGGAAC 420
GGGTTGGCCG CGGAGCTGAG TTCGGCGGCC ACCGGTTATG AGACGGTGAT CACTCAGCTC 480
AGCAGTGAGG GGTGGCTAGG TCCGGCGTCA GCGGCGATGG CCGAGGCAGT TGCGCCGTAT 540
GTGGCGTGGA TGAGTGCCGC TGCGGCGCAA GCCGAGCAGG CGGCCACACA GGCCAGGGCC 600
GCCGCGGCCG CTTTTGAGGC GGCGTTTGCC GCGACGGTGC CTCCGCCGTT GATCGCGGCC 660
AACCGGGCTT CGTTGATGCA GCTGATCTCG ACGAATGTCT TTGGTCAGAA CACCTCGGCG 720
ATCGCGGCCG CCGAAGCTCA GTACGGCGAG ATGTGGGCCC AAGACTCCGC GGCGATGTAT 780
GCCTACGCGG GCAGTTCGGC GAGCGCCTCG GCGGTCACGC CGTTTAGCAC GCCGCCGCAG 840
ATTGCCAACC CGACCGCTCA GGGTACGCAG GCCGCGGCCG TGGCCACCGC CGCCGGTACC 900
GCCCAGTCGA CGCTGACGGA GATGATCACC GGGCTACCCA ACGCGCTGCA AAGCCTCACC 960
TCACNTCTGT TGCAGTCGTC TAACGGTCCG CTGTCGTGGC TGTGGCAGAT CTTGTTCGGC 1020
ACGCCCAATT TCCCCACCTC AATTTCGGCA CTGCTGACCG ACCTGCAGCC CTACGCGAGC 1080
TTNTTNTATA ACACCGAGGG CCTGCCGTAC TTCAGCATCG GCATGGGCAA CAACTTCATT 1140
CAGTCGGCCA AGACCCTGGG ATTGATCGGC TAGGCGGCAC CGGCTGCGGT CGCGGNTGCT 1200
GGGGATNCCG CCAAGGGCTT GCCTCGTGCC G 1231
(2) INFORMATION FOR SEQ ID NO:105:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 2041 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: cDNA
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:105:
CGGCACGAGC TCGTGCCGAT CAGTGCCATT GACGGCTTGT ACGACCTTCT GGGGATTGGA 60
ATACCCAACC AAGGGGGTAT CCTTTACTCC TCACTAGAGT ACTTCGAAAA AGCCCTGGAG 120
GAGCTGGCAG CAGCGTTTCC GGGTGATGGC TGGTTAGGTT CGGCCGCGGA CAAATACGCC 180
GGCAAAAACC GCAACCACGT GAATTTTTTC CAGGAACTGG CAGACCTCGA TCGTCAGCTC 240
ATCAGCCTGA TCCACGACCA GGCCAACGCG GTCCAGACGA CCCGCGACAT CCTGGAGGGC 300
GCCAAGAAAG GTCTCGAGTT CGTGCGCCCG GTGGCTGTGG ACCTGACCTA CATCCCGGTC 360
GTCGGGCACG CCCTATCGGC CGCCTTCCAN GCGCCGTTTT GCGCGGGCGC GATGGCCGTA 420
GTGGGCGGCG CGCTTGCCTA CTTGGTCGTG AAAACGCTGA TCAACGCGAC TCAACTCCTC 480
AAATTGCTTG CCAAATTGGC GGAGTTGGTC GCGGCCGCCA TTGCGGACAT CATTTCGGAT 540
GTGGCGGACA TCATCAAGGG CATCCTCGGA GAAGTGTGGG AGTTCATCAC AAACGCGCTC 600
AACGGCCTGA AAGAGCTTTG GGACAAGCTC ACGGGGTGGG TGACCGGACT GTTCTCTCGA 660
GGGTGGTCGA ACCTGGAGTC CTTCTTTGCG GGCGTCCCCG GCTTGACCGG CGCGACCAGC 720
GGCTTGTCGC AAGTGACTGG CTTGTTCGGT GCGGCCGGTC TGTCCGCATC GTCGGGCTTG 780
GCTCACGCGG ATAGCCTGGC GAGCTCAGCC AGCTTGCCCG CCCTGGCCGG CATTGGGGGC 840
GGGTCCGGTT TTGGGGGCTT GCCGAGCCTG GCTCAGGTCC ATGCCGCCTC AACTCGGCAG 900
GCGCTACGGC CCCGAGCTGA TGGCCCGGTC GGCGCCGCTG CCGAGCAGGT CGGCGGGCAG 960
TCGCAGCTGG TCTCCGCGCA GGGTTCCCAA GGTATGGGCG GACCCGTAGG CATGGGCGGC 1020
ATGCACCCCT CTTCGGGGGC GTCGAAAGGG ACGACGACGA AGAAGTACTC GGAAGGCGCG 1080
GCGGCGGGCA CTGAAGACGC CGAGCGCGCG CCAGTCGAAG CTGACGCGGG CGGTGGGCAA 1140
AAGGTGCTGG TACGAAACGT CGTCTAACGG CATGGCGAGC CAAATCCATT GCTAGCCAGC 1200
GCCTAACAAC GCGCAATGCT AAACGGAAGG GACACGATCA ATGACGGAAA ACTTGACCGT 1260
CCAGCCCGAG CGTCTCGGTG TACTGGCGTC GCACCATGAC AACGCGGCGG TCGATGCNTC 1320
CTCGGGCGTC GAAGCTGCCG CTGGCCTAGG CGAATCTGTG GCGATCACTC ACGGTCCGTA 1380
CTGCTCACAG TTCAACGACA CGTTAAATGT GTACTTGACT GCCCACAATG CCCTGGGCTC 1440
GTCCTTGCAT ACGGCCGGTG TCGATCTCGC CAAAAGTCTT CGAATTGCGG CGAAGATATA 1500
TAGCGAGGCC GACGAAGCGT GGCGCAAGGC TATCGACGGG TTGTTTACCT GACCACGTTT 1560
GCTGCCCGCA GTGCAGGCCA CGACGTAGCG CAGGTCGTGT CCCTCGTAGG CGTGGATGCG 1620
ACCGGCCAGC ACCAGCACCC GGTGCGCACC GATGGGCACG GACAGTAGCT CGCCCGCATG 1680
CCCGGCTGCG GTTGGCGGCA CAAACCCGGG CAGTTCGGCC TGCGGCAGCA CGGTGGTNGG 1740
GGAGCCCAAC GCCGCAACGG CCGGTAACCA TCCCGACCCG AGCACGACCG AGACGTCATG 1800
TTCGCCGATC CCGGTGCGGT CAGCGATGAC CTGCGCCGCC CGCCGGGCCA GTTTGTCGGG 1860
ATCGGGGCGC GGGTCAGCCA CACTGGGCGA GCTTAACTGA GCCGCTCGCC GGGGAGCGGG 1920
TGCTNGTCGA TGAGATACTG CGAGCATGCC AGCAGCCAGC GCATCCGACC GCGTCGAGGA 1980
ATTGGTGCGG CGCCGTGGTG GCGAGCTGGT CGAGCTGTCC CATGCCATCC ACCTCGTGCC 2040
G 2041
(2) INFORMATION FOR SEQ ID NO:106:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 1202 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: cDNA
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:106:
GAGCTCACCG CTATCAACCA ATACTTTCTG CACTCCAAGA TGCAGGACAA CTGGGGTTTT 60
ACCGAGCTGG CGGCCCACAC CCGCGCGGAG TCGTTCGACG AAATGCGGCA CGCCGAGGAA 120
ATCACCGATC GCATCTTGTT GCTGGATGGT TTGCCGAACT ACCAGCGCAT CGGTTCGTTG 180
CGTATCGGCC AGACGCTCCG CGAGCAATTT GAGGCCGATC TGGCGATCGA ATACGACGTG 240
TTGAATCGTC TCAAGCCAGG AATCGTCATG TGCCGGGAGA AACAGGACAC CACCAGCGCC 300
GTACTGCTGG AGAAAATCGT TGCCGACGAG GAAGAACACA TCGACTACTT GGAAACGCAG 360
CTGGAGCTGA TGGACAAGCT AGGAGAGGAG CTTTACTCGG CGCAGTGCGT CTCTCGCCCA 420
CCGACCTGAT GCCCGCTTGA GGATTCTCCG ATACCACTCC GGGCGCCGCT GACAAGCTCT 480
AGCATCGACT CGAACAGCGA TGGGAGGGCG GATATGGCGG GCCCCACAGC ACCGACCACT 540
GCCCCCACCG CAATCCGAGC CGGTGGCCCG CTGCTCAGTC CGGTGCGACG CAACATTATT 600
TTCACCGCAC TTGTGTTCGG GGTGCTGGTC GCTGCGACCG GCCAAACCAT CGTTGTGCCC 660
GCATTGCCGA CGATCGTCGC CGAGCTGGGC AGCACCGTTG ACCAGTCGTG GGCGGTCACC 720
AGCTATCTGC TGGGGGGAAC ACTSKYGKKK KTGKKGKSKS KSRMRMKCTC GGTGATCTGC 780
TCGGCCGCAA CAGGGTGCTG CTAGGCTCCG TCGTGGTCTT CGTCGTTGGC TCTGTGCTGT 840
GCGGGTTATC GCAGACGATG ACCATGCTGG CGATCTCTCG CGCACTGCAG GGCGTCGGTG 900
CCGGTGCGAT TTCCGTCACC GCCTACGCGC TGGCCGCTGA GGTGGTCCCA CTGCGGGACC 960
GTGGCCGCTA CCAGGGCGTC TTANGTGCGG TGTTCGGTGT CAACACGGTC ACCGGTCCGC 1020
TGCTGGGGGG CTGGCTCACC GACTATCTGA GCTGGCGGTG GGCGTTCCGA CCACCAGCCC 1080
CATCACCGAC CCGATCGCGG TCATCGCGGC GAACACCGCC CTCGCGGCGT TGCGGGCAGG 1140
TCCCTTGGGG AACGTGGTCC CACAGCGCCA GAACGGTCGG AAATGCGATG GCCGACCCAC 1200
AC 1202
(2) INFORMATION FOR SEQ ID NO:107:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 496 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: cDNA
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:107:
GGCGGCGGCA GTTGGCCAGC AGTTNGGGCG GGGGAGCCGG TTCGGNGACC AAGAAATCGG 60
CCTGGGCAAG CAGCCGGGAC CGCGNACCGT GATCAGTTNG GATCGCCGGG ACCGCCGCCG 120
ACCAANGCCA TTCCGCCGNT GAGGAAGTCG GAANTNTGCG CAGTGATGAC GCCCTGCTGC 180
AACGCNTCCC GGATTGCCGA GCGGATCGCC GCCGAACGGC GGTGCTCACC ACCGGCGAGC 240
ACCCCTACNG ACAGGCCCGC ATAGCTGAAT GACGCCGGGT NACCGCCGTC CCNTCCACCG 300
NGANATCGGC CCGGANGCAA AAGATCCGTC GGCGCTCCGC CTCGGCGACG ACAGCCACGT 360
TCACCCGCGC GTTATCGGTG GCCGCGATCG CATACCAGGC GCCGTCAAGG TNGCCGTYGC 420
GGTAGTCACG CACCGACAAG GTGATYTGGT CCATCGCCTN GACGGCGGGG GTGACGCTGG 480
GGGCGATCAM GTGCAC 496
(2) INFORMATION FOR SEQ ID NO:108:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 849 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: cDNA
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:108:
TGGATTCCGA TAGCGGTTTC GGCCCCTCGA CGGGCGACCA CGGCGCGCAG GCCTCCGAAC 60
GGGGGGCCGG GACGCTGGGA TTCGCCGGGA CCGCAACCAA AGAACGCCGG GTCCGGGCGG 120
TCGGGCTGAC CGCACTGGCC GGTGATGAGT TCGGCAACGG CCCCCGGATG CCGATGGTGC 180
CGGGGACCTG GGAGCAGGGC AGCAACGAGC CCGAGGCGCC CGACGGATCG GGGAGAGGGG 240
GAGGCGACGG CTTACCGCAC GACAGCAAGT AACCGAATTC CGAATCACGT GGACCCGTAC 300
GGGTCGAAAG GAGAGATGTT ATGAGCCTTT TGGATGCTCA TATCCCACAG TTGGTGGCCT 360
CCCAGTCGGC GTTTGCCGCC AAGGCGGGGC TGATGCGGCA CACGATCGGT CAGGCCGAGC 420
AGGCGGCGAT GTCGGCTCAG GCGTTTCACC AGGGGGAGTC GTCGGCGGCG TTTCAGGCCG 480
CCCATGCCCG GTTTGTGGCG GCGGCCGCCA AAGTCAACAC CTTGTTGGAT GTCGCGCAGG 540
CGAATCTGGG TGAGGCCGCC GGTACCTATG TGGCCGCCGA TGCTGCGGCC GCGTCGACCT 600
ATACCGGGTT CTGATCGAAC CCTGCTGACC GAGAGGACTT GTGATGTCGC AAATCATGTA 660
CAACTACCCC GCGATGTTGG GTCACGCCGG GGATATGGCC GGATATGCCG GCACGCTGCA 720
GAGCTTGGGT GCCGAGATCG CCGTGGAGCA GGCCGCGTTG CAGAGTGCGT GGCAGGGCGA 780
TACCGGGATC ACGTATCAGG CGTGGCAGGC ACANTGGTAA CCANGCCANG GAAGATTTGG 840
TGCGGGCCT 849
(2) INFORMATION FOR SEQ ID NO:109:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 97 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: protein
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:109:
Met Ser Leu Leu Asp Ala His Ile Pro Gln Leu Val Ala Ser Gln Ser
1 5 10 15
Ala Phe Ala Ala Lys Ala Gly Leu Met Arg His Thr Ile Gly Gln Ala
20 25 30
Glu Gln Ala Ala Met Ser Ala Gln Ala Phe His Gln Gly Glu Ser Ser
35 40 45
Ala Ala Phe Gln Ala Ala His Ala Arg Phe Val Ala Ala Ala Ala Lys
50 55 60
Val Asn Thr Leu Leu Asp Val Ala Gln Ala Asn Leu Gly Glu Ala Ala
65 70 75 80
Gly Thr Tyr Val Ala Ala Asp Ala Ala Ala Ala Ser Thr Tyr Thr Gly
85 90 95
Phe
(2) INFORMATION FOR SEQ ID NO:110:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:110:
Met Ser Leu Leu Asp Ala His Ile Pro Gln Leu Val Ala Ser Gln
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:111:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:111:
Ala His Ile Pro Gln Leu Val Ala Ser Gln Ser Ala Phe Ala Ala
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:112:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:112:
Leu Val Ala Ser Gln Ser Ala Phe Ala Ala Lys Ala Gly Leu Met
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:113:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:113:
Ser Ala Phe Ala Ala Lys Ala Gly Leu Met Arg His Thr Ile Gly
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:114:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:114:
Lys Ala Gly Leu Met Arg His Thr Ile Gly Gln Ala Glu Gln Ala
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:115:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:115:
Arg His Thr Ile Gly Gln Ala Glu Gln Ala Ala Met Ser Ala Gln
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:116:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:116:
Gln Ala Glu Gln Ala Ala Met Ser Ala Gln Ala Phe His Gln Gly
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:117:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:117:
Ala Met Ser Ala Gln Ala Phe His Gln Gly Glu Ser Ser Ala Ala
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:118:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:118:
Ala Phe His Gln Gly Glu Ser Ser Ala Ala Phe Gln Ala Ala His
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:119:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:119:
Glu Ser Ser Ala Ala Phe Gln Ala Ala His Ala Arg Phe Val Ala
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:120:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:120:
Phe Gln Ala Ala His Ala Arg Phe Val Ala Ala Ala Ala Lys Val
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:121:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:121:
Ala Arg Phe Val Ala Ala Ala Ala Lys Val Asn Thr Leu Leu Asp
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:122:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:122:
Ala Ala Ala Lys Val Asn Thr Leu Leu Asp Val Ala Gln Ala Asn
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:123:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 15 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:123:
Asn Thr Leu Leu Asp Val Ala Gln Ala Asn Leu Gly Glu Ala Ala
1 5 10 15
(2) INFORMATION FOR SEQ ID NO:124:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 18 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:124:
Val Ala Gln Ala Asn Leu Gly Glu Ala Ala Gly Thr Tyr Val Ala Ala
1 5 10 15
Asp Ala
(2) INFORMATION FOR SEQ ID NO:125:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 1752 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: cDNA
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:125:
CGGCACGAGA ATGTCGCCTG TGCCTCGATA GCCACTTGCG TGTGGTCGCG CTGCCAGCGG 60
GTCAGCCAGG TCGCCTGGTC CAGGCCATCG GGCCGGCGCA GGAGCGCGAT GTTGGCCAGA 120
CCCGGTGTAC GAGAACCGGA CTCGACNAAG TGTCGGCGCT GACGGCGGCT CAGTTCGCGG 180
CACACGCCCA GATCTATCAG GCCGTCAGCG CCCAGGCCGC GGCGATTCAC GAGATGTTCG 240
TCAACACTCT ACAGATNANC TCAGGGTCGT ATGCTGCTAC CGAGGCCGCC AACGCGGCCG 300
CGGCCGGCTA GAGGAGTCAC TGCGATGGAT TTTGGGGCGT TGCCGCCGGA GGTCAATTCG 360
GTGCGGATGT ATGCCGGTCC TGGCTCGGCA CCAATGGTCG CTGCGGCGTC GGCCTGGAAC 420
GGGTTGGCCG CGGAGCTGAG TTCGGCGGCC ACCGGTTATG AGACGGTGAT CACTCAGCTC 480
AGCAGTGAGG GGTGGCTAGG TCCGGCGTCA GCGGCGATGG CCGAGGCAGT TGCGCCGTAT 540
GTGGCGTGGA TGAGTGCCGC TGCGGCGCAA GCCGAGCAGG CGGCCACACA GGCCAGGGCC 600
GCCGCGGCCG CTTTTGAGGC GGCGTTTGCC GCGACGGTGC CTCCGCCGTT GATCGCGGCC 660
AACCGGGCTT CGTTGATGCA GCTGATCTCG ACGAATGTCT TTGGTCAGAA CACCTCGGCG 720
ATCGCGGCCG CCGAAGCTCA GTACGGCGAG ATGTGGGCCC AAGACTCCGC GGCGATGTAT 780
GCCTACGCGG GCAGTTCGGC GAGCGCCTCG GCGGTCACGC CGTTTAGCAC GCCGCCGCAG 840
ATTGCCAACC CGACCGCTCA GGGTACGCAG GCCGCGGCCG TGGCCACCGC CGCCGGTACC 900
GCCCAGTCGA CGCTGACGGA GATGATCACC GGGCTACCCA ACGCGCTGCA AAGCCTCACC 960
TCACNTCTGT TGCAGTCGTC TAACGGTCCG CTGTCGTGGC TGTGGCAGAT CTTGTTCGGC 1020
ACGCCCAATT TCCCCACCTC AATTTCGGCA CTGCTGACCG ACCTGCAGCC CTACGCGAGC 1080
TTNTTNTATA ACACCGAGGG CCTGCCGTAC TTCAGCATCG GCATGGGCAA CAACTTCATT 1140
CAGTCGGCCA AGACCCTGGG ATTGATCGGC TAGGCGGCAC CGGCTGCGGT CGCGGCTGCT 1200
GGGGATGCCG CCAAGGGCTT GCCTGGACTG GGCGGGATGC TCGGTGGCGG GCCGGTGGCG 1260
GCGGGTCTGG GCAATGCGGC TTCGGTTGGC AAGCTGTCGG TGCCGCCGGT GTGGANTGGA 1320
CCGTTGCCCG GGTCGGTGAC TCCGGGGGCT GCTCCGCTAC CGGTGAGTAC GGTCAGTGCC 1380
GCCCCGGAGG CGGCGCCCGG AAGCCTGTTG GGCGGCCTGC CGCTANCTGG TGCGGGCGGG 1440
GCCGGCGCGG GTCCACGCTA CGGATTCCRT CCCACCGTCA TGGCTCGCCC ACCCTTCGMC 1500
GGGATAGTCG CTGCCGCAAC GTATTAACGC GCCGGCCTCG GCTGGTGTGG TCCGCTGCGG 1560
GTGGCAATTG GTCNGCGCCG AAATCTCSGT GGGTTATTTR CGGTGGGATT TTTTCCCGAA 1620
GCCGGGTTCA RCACCGGATT TCCTAACGGT CCCGCKACTC TCGTGCCGAA TTCSGCACTA 1680
AGTGACGTCC GGCGGAAACC CGTTGGGTNT GAAAGCTTCA GAAAGGCCCG CTCCCAGGGG 1740
TTCGGCAAAC GG 1752
(2) INFORMATION FOR SEQ ID NO:126:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 400 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: protein
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:126:
Met Asp Phe Gly Ala Leu Pro Pro Glu Val Asn Ser Val Arg Met Tyr
1 5 10 15
Ala Gly Pro Gly Ser Ala Pro Met Val Ala Ala Ala Ser Ala Trp Asn
20 25 30
Gly Leu Ala Ala Glu Leu Ser Ser Ala Ala Thr Gly Tyr Glu Thr Val
35 40 45
Ile Thr Gln Leu Ser Ser Glu Gly Trp Leu Gly Pro Ala Ser Ala Ala
50 55 60
Met Ala Glu Ala Val Ala Pro Tyr Val Ala Trp Met Ser Ala Ala Ala
65 70 75 80
Ala Gln Ala Glu Gln Ala Ala Thr Gln Ala Arg Ala Ala Ala Ala Ala
85 90 95
Phe Glu Ala Ala Phe Ala Ala Thr Val Pro Pro Pro Leu Ile Ala Ala
100 105 110
Asn Arg Ala Ser Leu Met Gln Leu Ile Ser Thr Asn Val Phe Gly Gln
115 120 125
Asn Thr Ser Ala Ile Ala Ala Ala Glu Ala Gln Tyr Gly Glu Met Trp
130 135 140
Ala Gln Asp Ser Ala Ala Met Tyr Ala Tyr Ala Gly Ser Ser Ala Ser
145 150 155 160
Ala Ser Ala Val Thr Pro Phe Ser Thr Pro Pro Gln Ile Ala Asn Pro
165 170 175
Thr Ala Gln Gly Thr Gln Ala Ala Ala Val Ala Thr Ala Ala Gly Thr
180 185 190
Ala Gln Ser Thr Leu Thr Glu Met Ile Thr Gly Leu Pro Asn Ala Leu
195 200 205
Gln Ser Leu Thr Ser Xaa Leu Leu Gln Ser Ser Asn Gly Pro Leu Ser
210 215 220
Trp Leu Trp Gln Ile Leu Phe Gly Thr Pro Asn Phe Pro Thr Ser Ile
225 230 235 240
Ser Ala Leu Leu Thr Asp Leu Gln Pro Tyr Ala Ser Xaa Xaa Tyr Asn
245 250 255
Thr Glu Gly Leu Pro Tyr Phe Ser Ile Gly Met Gly Asn Asn Phe Ile
260 265 270
Gln Ser Ala Lys Thr Leu Gly Leu Ile Gly Ser Ala Ala Pro Ala Ala
275 280 285
Val Ala Ala Ala Gly Asp Ala Ala Lys Gly Leu Pro Gly Leu Gly Gly
290 295 300
Met Leu Gly Gly Gly Pro Val Ala Ala Gly Leu Gly Asn Ala Ala Ser
305 310 315 320
Val Gly Lys Leu Ser Val Pro Pro Val Trp Xaa Gly Pro Leu Pro Gly
325 330 335
Ser Val Thr Pro Gly Ala Ala Pro Leu Pro Val Ser Thr Val Ser Ala
340 345 350
Ala Pro Glu Ala Ala Pro Gly Ser Leu Leu Gly Gly Leu Pro Leu Xaa
355 360 365
Gly Ala Gly Gly Ala Gly Ala Gly Pro Arg Tyr Gly Phe Xaa Pro Thr
370 375 380
Val Met Ala Arg Pro Pro Phe Xaa Gly Ile Val Ala Ala Ala Thr Tyr
385 390 395 400
(2) INFORMATION FOR SEQ ID NO:127:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 474 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: cDNA
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:127:
GGCACGAGCA CCAGTTGACC CGCGAAGAAC CTGACCGCGC CACCCAGCGC CGCCCGCATC 60
ACCGGCCCCG TCCCACGAAC CTTTTCGGTA AACGAGCCAC TCCAGCGGAG ATCGGTACCG 120
CCCGACGCAT TTGGTGTAAG GACCACCTCG CCGAAGTAGT CCTGGACGGG TGTCCTCGCG 180
CCAACCAGCT TGTAGACGTG GCGACGGTCC TGCTCATACT CGACGGTCTC TTCCTGCACG 240
AACACCGGCC ACATGCCTAG TTTGCGGATG GCCCCGATGC CGCCGGGCGC GGGATCACCG 300
CGTCGCGCCC AACTCGATTG AGCAACGATG GGCTTGGCCC AGGTCGCCCA GTTGCCACCG 360
TCTGTCACGA GCCGAAACAA GGTTGCAGCC GGCGCGCTGC TGGTCTTGGT GACCTCGAAC 420
GAAAATTTCC GACCCGACAT GCGCGACTCC CGAAACGACA ACTGAAGCTC GTGC 474
(2) INFORMATION FOR SEQ ID NO:128:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 1431 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: cDNA
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:128:
CTGCGCGCCG GAAAAAANTA TTACTGGCAG GACCGGCAGA ATGCATGGTG ATATTCCGGT 60
GATGAGGCCG CCGAGGAACC GACTAGTGCG AGGGTCAACA CATCGGTTAT TCGTTGCCGT 120
TTAGGTCTTG GATCTGCCGG GACGGCAACG AGTTGGCAGG ACCGCTCACG CGAGCGCTGT 180
TGACAGAGTC GGTTCACGTC GAACTCGCCA CCCGTCAGAT GCGAATGATA GCCACATCGG 240
CCACACCATC GACGGCGTCG AAGTCGCCGT CGTGGGTCAC GACCGGCACC CCTTGCGACG 300
TGGCAACGGC AGCGGCCCTC ACCGGACGGG ACCGAGATCG TCGGTGGTGT CGCCAGTGAG 360
CGTTGCGAGG TCGCGGGTGC AATCCCGCAT CTGCTTGCGT ATGCCGAAGC CGCCGCAGCA 420
GCTCGTCTCG ACTCAACCAT CGGCGCCGTG CGGGCTGCCT GCGGTCAGCA GCGCAACGGG 480
TTTGCCGTTG GCAGTGATGG TGATGTCTTC GCCGGCCTGC ACGCGCCGTA GCAGCCCGGC 540
GGTGTTGTTG CGCAGTTCGC GAGACGCGAC TTCAGCAGGC ATGCTGCGGG GATCGGCTTG 600
CGCTGGGCGC GGTGTCACCG TCATGCGCTT GGGATATCAC GTGATCTATC GGCACGAAGC 660
CGCCGGATGA GCGAGGCAAA CCGCCTACAC GGGCTGCCTC GCCTTGACCG CGCCGAACGT 720
TACTGTGCCG GGGGCATCAG CACCGTATCG ATCATGTACA CCGTCGCGTG GGCGGTGTGA 780
CTCCGCCACA TACCAAACGG GCGTTGTTGA CCATGAGTCG TCGCGGGCGC CTATCACCGT 840
CAGGTCGGCA CCTTGCAGGT CTGATGGGTG CCGTCGATCC TGCTCGGACT CGCCTGGCCG 900
GCTATCACGT GGTAGGTCAG GATGCTGCTG AGCAGCTTGG CGTCAGTCTT GAGTTGATCG 960
ATAGTGGCCG CCGGCAGCTT GTCGAATGCG GCGTTGGTGG GGGCGAAAAC GGTGTACTCG 1020
CCGCCGTTGA GGGTGTCGAC CAGATTCACA TCCGGGTTCA GCTTGCCCGA CAGAGCCGAG 1080
GTCAGGGTAC TGAGCATCGG GTTGTTGGAA GCCGCGGTAG CGACCGGGTC TTGCGCCATT 1140
CCGGCCACCG ATCCGGGACC GGTGGGATTT TGCGCCGCGT ATTGCGCGCA CCCACGACCA 1200
ATCAGGTCCG CTGCGGTCAG CCATTGCCGC CGTGGTAACG GGCGCCGCCG GGCTGGTCGC 1260
CGGTTTCGGG CTGGTGTCTT GCGACACGGG TTTGGTGCTC GAACAACCCG CTAAGAACGC 1320
AATCGCGATG GCTGCGAGGC TCGCTGCTGC GGCCGGTTTG GCCTGAACGT TGATCATCGC 1380
TTCGATTCCT TTGCTTCTGC GGCGGCGTTG AACGCCGTCC TCCTGGGTGG A 1431
(2) INFORMATION FOR SEQ ID NO:129:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 279 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: cDNA
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:129:
GCACGAGAGT CGTATCTTTG CACCCAGCGC CCGTAGGAAA CCGCTGGCCT GGCTAACTCA 60
GATGCGGGCG GCCGTCGATT CGAGAGGTAA CCGATCGCCC GCCGACAATG GGTTACCCAC 120
CGAGACTGAT TGCCGCGCAG CCGCCTTCGA CGTGTAAGCG CCGGTTCGTG CATGCCCGGA 180
ACGGCTGCAC TCACGGACCT TCTACGTAGT ACGTGACGGA CTTTTACGCA TTATCGCTGA 240
CGATCTTTGC CTCCCAGGAC TCCAGAATCT ACTCGTGCC 279
(2) INFORMATION FOR SEQ ID NO:130:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 1470 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: cDNA
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:130:
ACCGCCACCC GCAGCCCGGA ATCACCGTCG GTAACCTGCG AATACAATTT CTTCATCGAC 60
GACTTCGCGA ACAGCGAACC CGAGCCCACC GCCTGATAGC CTTCTTCCTC GATGTTCCAA 120
CCGCCGGCGG CGTCGAACGA AACGATACGA CCCGCGCTCT GCGGGTCAGA CGCATGAATG 180
TCGTAGCCCG CCAGCAACGG CAACGCCAGC AGACCCTGCA TCGCGGCCGC CAGATTGCCA 240
CGCACCATAA TCGCCAGCCG GTTGATTTTG CCGGCAAACG TCAGCGGCAC ACCCTCGAGC 300
TTCTCGTAGT GCTCAAGTTC CACGGCATAC AGCCGGGCAA ACTCAACCGC GACCGCAGCC 360
GTGCCAGCGA TGCCGGTAGC GGTGTAGTCA TCGGTGATAT ACACCTTGCG CACATCACGC 420
CCAGAAATCA TGTTGCCCTG CGTCGAACGC CGGTCACCCG CCATGACAAC ACCGCCGGGG 480
TATTTCAGCG CGACAATGGT GGTGCCGTGC GGCAGTTGCG CATCGCCGCC TGCGAGTGGC 540
GCACCGCCGC TGATGCTTGC CGGCAGCAAC TCCGGCGCCT GGCGGCGCAG GAAGTCAAGT 600
GAAAGAAGAT AGGTCTACAG CGGGTGTTCC AGAGAGTGAA TTAATGGACA GGCGATCGGG 660
CAACGGCCAG GTCACTGTCC GCCCTTTTGG ACGTATGCGC GGACGAAGTC CTCGGCGTTC 720
TCCTCGAGGA CGTCGTCGAT TTCGTCGAGC AGATCGTCGG TCTCCTCGGT CAGCTTTTCG 780
CGACGCTCCT GGCCCGCGGC GGTGCTGCCG GCGATGTCGT CATCATCGCC GCCGCCACCG 840
CCACGCTTGG TCTGCTCTTG CGCCATCGCC GCCTCCTGCT TCCTCATGGC CTTTCAAAAG 900
GCCGCGGGTG CGCGTCACAC GCCCGCTGTC TTTCTCTCAC CTACCGGTCA ACACCAACGT 960
TTCCCGGCCT AACCAGGCTT AGCGAGGCTC AGCGGTCAGT TGCTCTACCA GCTCCACGGC 1020
ACTGTCCACC GAATCCAGCA ACGCACCAAC ATGCGCCTTA CTACCCCGCA ACGGCTCCAG 1080
CGTCGGGATG CGAACCAGCG AGTCGCCGCC AGGTCGAAGA TCACCGAGTC CCAGCTAGCC 1140
GCGGCGATAT CAGCCCCGAA CCGGCGCAGG CATTTCGCCG CGGAAATACG CGCGGGTGTC 1200
GGTCGGCGGT TCTCCACCGC ACTCAGCACC TGGTGTTTCG GTGACTAAAC GCTTTATCGA 1260
GCCGCGCGCG ACCAGCCGGT TGTACAGGCC CTTGTCCAGC CGGACATCGG AGTACTGCAG 1320
GTTGACGAGG TGCAGCCGGG GCGCCGACCA GCTCAGGTTC TCCCGCTGCC GGAAACCGTC 1380
GAGCAGCCGC AGTTTGGCCG GCCAGTCCAG CAGCTCCGCG CAATCCATCG GGTCACGCTC 1440
GAGCTGATCC AGCACGTGTG CCCAGGTTTC 1470
(2) INFORMATION FOR SEQ ID NO:131:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 1059 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: cDNA
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:131:
ATTCCCATCG CTCCGGCACC TATCACCAGG TAGTCGGTTT CGATGGTTTT CGCCGGCCCT 60
TGCGTTGGCC TGGGCCACGG GTCGTTCATG GGCCCTCCTG TGCGGATTGG AATTTGTGAC 120
AACGAAATCG GGCGATCGGT GAGCAATCGT CGCCGATGCA AGACACGCTT TCGCTGCCGC 180
GGCGTCAGGT GGAGTTTAGG CCAGCGTAAC AACGTAGACC GGCCACTGAC CAAACCCCAA 240
ACCCACAAAC CCTGGACGCA TGCGGGTCTC GGGCGTCAAA TTCCGGGTAG ATATCGTATA 300
CCGATATCGG ATGCCGTAGC CTTATCGAGG CATGAGACGC CCGCTAGACC CACGCGATAT 360
TCCAGATGAG CTGCGGCGAC GGCTGGGGCT CTTGGATGCG GTGGTGATCG GGCTTGGGTC 420
CATGATCGGT GCCGGAATCT TTGCTCGTGC CGAATTCGGC ACGAGCTCGT GCCGAATTCG 480
GCACGAGATT CCAATCCCCA GAAGGTCGTA CAAGCCGTCA ATGGCACTTG ATCGTTGGAT 540
CGATGATGAA CGCTCTGCTC ATGCCTGCCG CCTATCTCAA CGGTCGTCGA TTCCATGCAT 600
TAGCCTTGGT TCTGCATTGC ACGCGTAGGG CCTACAGTCT GGCTGTCATG CTTGGCCGAT 660
GTCAACAGTT TTTTTCATGC TAAGCAGATC GTCAGTTTTG AGTTCGTGAA GACGGCATGT 720
TCACTTGTTG TCGACTACAT CGTCTGCGCA CATTTGCCCT CCTGCAACTG CGCTGCGACA 780
ATGCGCCAAC CGCCGTGTAG CTCGTGCCGA ATTCGGCACG AGGATCCACC GGAGATGGCC 840
GACGACTACG ACGAGGCCTG GATGCTCAAC ACCGTGTTCG ACTATCACAA CGAGAACGCA 900
AAAGAAGAGG TCATCCATCT CGTGCCCGAC GTGAACAAGG AGAGGGGGCC CATCGAACTC 960
GTAACCAAGG TAGACAAAGA GGGACATCAG ACTCGTCTAC GATGGGGAGC CACGTTTTCA 1020
TACAAGGAAC ATCCTAAGTT TTGATTCGGG AACATCCTA 1059
(2) INFORMATION FOR SEQ ID NO:132:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 153 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: cDNA
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:132:
GCACGAGGCA TTGGCGGGCA TCTGCATAAA CGGTGACGTA TCAGCACAAA ACAGCGGAGA 60
GAACAACATG CGATCAGAAC GTCTCCGGTG GCTGGTAGCC GCAGAAGGTC CGTTCGCCTC 120
GGTGTATTTC GACGACTCGC ACGACTCGTG CCG 153
(2) INFORMATION FOR SEQ ID NO:133:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 387 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: cDNA
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:133:
CCGCGCGGTC GATCAGCGAG CCAGGCAAAA ACTCCGTCGA GCCCGAGTCG ATGATGGTCA 60
CCCGGCGCAG CATCTGGCGA ACGATCACCT CGATGTGCTT GTCGTGGATC GACACACCTT 120
GGGCGCGGTA GACCTCCTGG ACCTCGCGAA CCAGGTGTAT CTGCACCTCG CGGGGGCCCT 180
GCACCCGCAG CACCTCATGC GGGTCGGCCG AGCCTTCCAT CAGCTGCTGG CCCACCTCGA 240
CGTGGTCGCC ATCGGAGAGC ACCCGTTCGG AACCGTCTTC GTGCTTGAAC ACCCGCAGCC 300
GCTGCCGCTT GGAGATCTTG TCGTAGACCA CTTCCTCACC GCCGTCGTCA GGAACGATGG 360
TGATCTTGTA GAACCGCTCG CCGTCCT 387
(2) INFORMATION FOR SEQ ID NO:134:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 389 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: cDNA
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:134:
GTTCAGCACG GCTATCCGAT TGTGCCGTTC GCTTCGGTGG GTGCTGAACA CGGCATCGAC 60
ATCGTGCTCG ACAACGAATC CCCACTGCTG GCACCGGTCC AGTTCCTCGC CGAGAAGCTG 120
CTCGGCACCA AAGACGGTCC GGCGCTGGTC CGTGGTGTCG GACTGACACC GGTACCGCGC 180
CCCGAACGGC AGTATTACTG GTTCGGCGAG CCAACCGACA CCACAGAGTT TATGGGGCAG 240
CAAGCCGACG ATAACGCCGC ACGCAGGGTG CGCGAGCGTG CCGCCGCCGC TATCGAACAC 300
GGCATCGAGC TGATGCTGGC CGAGCGCGCA GCCGATCCAA ATCGATCCCT GGTCGGACGG 360
CTCTTGCGCT CGGACGCCTA AGGCGCCCC 389
(2) INFORMATION FOR SEQ ID NO:135:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 480 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: cDNA
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:135:
CCCGCGGTCG GAATGATCCC CGTCTCGTCG CGCGCCCATT TGATGCTGTT GATGAGCTGT 60
TTGGAGAAGC CCGGTTGGCG TACCGGTGAG CCGGAATATC TGTTGGAAGC GTCACCGGAT 120
GTNCACATGA ANTNCNTTGN CCCNGTNGCG GTNTTGGNTG NGGNAAACAC GTGTTGTNTA 180
AGCCTTGNTG GNCTCGNAAG NGCCGTNGAC GCCTGTGTCG CCGAAGATAA TGAGCACCTG 240
ACGGTTGGCG GGATCGCCGT TATCCCAAGG AATTCCGAGG TCGGTCCCGG AGATGCCGAA 300
GCGTTCCAGG GTCTTGTTGG GGCTGTCCGG TCCGGTCACC CACTCGGCGA GGGATGTGGN 360
AGCCCCGGCG AGCGTGGCAC CAGGATCCGG CGCCGCCGCC GGAGCAGGGT CGGNNGCTGN 420
NCTGNNTTCC TNNNGCCNAA TTNNACTCCN NCNACAANCT TGNNNCCGAC TCNNACCCGN 480
(2) INFORMATION FOR SEQ ID NO:136:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 587 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: cDNA
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:136:
GCACGAGGCT ACCGGCGCGT CGCCCGCCAT GCCCTGGATG CACGCGTAGC CACCCGTNCA 60
TNCAGCGGGT CAGCCGCCGC GTCCGGGCTT AACGCTATAG CAGCTGCAAA CAACCCAGCG 120
CCGGCAATTA CTTTGATGTT GAACCGATGA CCATNGCCTN CGNGTNCAAT CTCNTCTCTT 180
NGCGCGCCNC TATTTNNGCC ATANATTTGG TTNNANNCGN AACGCTAGAC GTATCGAGTT 240
CCTTTTCGAC CACCGGCTCA ATTGTCAGCA TCCTATGGGG AACATGAGCC CCGCCGCACC 300
GGGCCGTTTC CAAATGGTGA CGTCACAACG GTGTCACAAG CCAGCGCAAT GTCCGCGGTA 360
GGGACGCGGC GGCTGGGATC GGTGGGGTGA GCGCCCGGCT TCTCAAAGCG AGGGGAGCCC 420
CGGGACTCTT ACCGGCCGAA GGCGGCGGGT GTCACTGATC TAGGCTGACG GCCAGTGGTT 480
GNTNAGCCAA CAAGGATGAC NACAAATAAN CCGAGGANAG ACANGNGACG GNCCGANANG 540
CTNANCCGGN NTTGNNCNAA NNNNACNCAC TTNTACCGNN CTTATGN 587
(2) INFORMATION FOR SEQ ID NO:137:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 1200 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: cDNA
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:137:
CAGGCATGAG CAGAGCGTTC ATCATCGATC CAACGATCAG TGCCATTGAC GGCTTGTACG 60
ACCTTCTGGG GATTGGAATA CCCAACCAAG GGGGTATCCT TTACTCCTCA CTAGAGTACT 120
TCGAAAAAGC CCTGGAGGAG CTGGCAGCAG CGTTTCCGGG TGATGGCTGG TTAGGTTCGG 180
CCGCGGACAA ATACGCCGGC AAAAACCGCA ACCACGTGAA TTTTTTCCAG GAACTGGCAG 240
ACCTCGATCG TCAGCTCATC AGCCTGATCC ACGACCAGGC CAACGCGGTC CAGACGACCC 300
GCGACATCCT GGAGGGCGCC AAGAAAGGTC TCGAGTTCGT GCGCCCGGTG GCTGTGGACC 360
TGACCTACAT CCCGGTCGTC GGGCACGCCC TATCGGCCGC CTTCCAGGCG CCGTTTTGCG 420
CGGGCGCGAT GGCCGTAGTG GGCGGCGCGC TTGCCTACTT GGTCGTGAAA ACGCTGATCA 480
ACGCGACTCA ACTCCTCAAA TTGCTTGCCA AATTGGCGGA GTTGGTCGCG GCCGCCATTG 540
CGGACATCAT TTCGGATGTG GCGGACATCA TCAAGGGCAC CCTCGGAGAA GTGTGGGAGT 600
TCATCACAAA CGCGCTCAAC GGCCTGAAAG AGCTTTGGGA CAAGCTCACG GGGTGGGTGA 660
CCGGACTGTT CTCTCGAGGG TGGTCGAACC TGGAGTCCTT CTTTGCGGGC GTCCCCGGCT 720
TGACCGGCGC GACCAGCGGC TTGTCGCAAG TGACTGGCTT GTTCGGTGCG GCCGGTCTGT 780
CCGCATCGTC GGGCTTGGCT CACGCGGATA GCCTGGCGAG CTCAGCCAGC TTGCCCGCCC 840
TGGCCGGCAT TGGGGGCGGG TCCGGTTTTG GGGGCTTGCC GAGCCTGGCT CAGGTCCATG 900
CCGCCTCAAC TCGGCAGGCG CTACGGCCCC GAGCTGATGG CCCGGTCGGC GCCGCTGCCG 960
AGCAGGTCGG CGGGCAGTCG CAGCTGGTCT CCGCGCAGGG TTCCCAAGGT ATGGGCGGAC 1020
CCGTAGGCAT GGGCGGCATG CACCCCTCTT CGGGGGCGTC GAAAGGGACG ACGACGAAGA 1080
AGTACTCGGA AGGCGCGGCG GCGGGCACTG AAGACGCCGA GCGCGCGCCA GTCGAAGCTG 1140
ACGCGGGCGG TGGGCAAAAG GTGCTGGTAC GAAACGTCGT CTAACGGCAT GGCGAGCCAA 1200
(2) INFORMATION FOR SEQ ID NO:138:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 392 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: protein
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:138:
Met Ser Arg Ala Phe Ile Ile Asp Pro Thr Ile Ser Ala Ile Asp Gly
1 5 10 15
Leu Tyr Asp Leu Leu Gly Ile Gly Ile Pro Asn Gln Gly Gly Ile Leu
20 25 30
Tyr Ser Ser Leu Glu Tyr Phe Glu Lys Ala Leu Glu Glu Leu Ala Ala
35 40 45
Ala Phe Pro Gly Asp Gly Trp Leu Gly Ser Ala Ala Asp Lys Tyr Ala
50 55 60
Gly Lys Asn Arg Asn His Val Asn Phe Phe Gln Glu Leu Ala Asp Leu
65 70 75 80
Asp Arg Gln Leu Ile Ser Leu Ile His Asp Gln Ala Asn Ala Val Gln
85 90 95
Thr Thr Arg Asp Ile Leu Glu Gly Ala Lys Lys Gly Leu Glu Phe Val
100 105 110
Arg Pro Val Ala Val Asp Leu Thr Tyr Ile Pro Val Val Gly His Ala
115 120 125
Leu Ser Ala Ala Phe Gln Ala Pro Phe Cys Ala Gly Ala Met Ala Val
130 135 140
Val Gly Gly Ala Leu Ala Tyr Leu Val Val Lys Thr Leu Ile Asn Ala
145 150 155 160
Thr Gln Leu Leu Lys Leu Leu Ala Lys Leu Ala Glu Leu Val Ala Ala
165 170 175
Ala Ile Ala Asp Ile Ile Ser Asp Val Ala Asp Ile Ile Lys Gly Thr
180 185 190
Leu Gly Glu Val Trp Glu Phe Ile Thr Asn Ala Leu Asn Gly Leu Lys
195 200 205
Glu Leu Trp Asp Lys Leu Thr Gly Trp Val Thr Gly Leu Phe Ser Arg
210 215 220
Gly Trp Ser Asn Leu Glu Ser Phe Phe Ala Gly Val Pro Gly Leu Thr
225 230 235 240
Gly Ala Thr Ser Gly Leu Ser Gln Val Thr Gly Leu Phe Gly Ala Ala
245 250 255
Gly Leu Ser Ala Ser Ser Gly Leu Ala His Ala Asp Ser Leu Ala Ser
260 265 270
Ser Ala Ser Leu Pro Ala Leu Ala Gly Ile Gly Gly Gly Ser Gly Phe
275 280 285
Gly Gly Leu Pro Ser Leu Ala Gln Val His Ala Ala Ser Thr Arg Gln
290 295 300
Ala Leu Arg Pro Arg Ala Asp Gly Pro Val Gly Ala Ala Ala Glu Gln
305 310 315 320
Val Gly Gly Gln Ser Gln Leu Val Ser Ala Gln Gly Ser Gln Gly Met
325 330 335
Gly Gly Pro Val Gly Met Gly Gly Met His Pro Ser Ser Gly Ala Ser
340 345 350
Lys Gly Thr Thr Thr Lys Lys Tyr Ser Glu Gly Ala Ala Ala Gly Thr
355 360 365
Glu Asp Ala Glu Arg Ala Pro Val Glu Ala Asp Ala Gly Gly Gly Gln
370 375 380
Lys Val Leu Val Arg Asn Val Val
385 390
(2) INFORMATION FOR SEQ ID NO:139:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 439 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: cDNA
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:139:
ACGTTTACCC ATGCCGTCGG TGCAGAGCAA CGCCAGACAA CACAAAGTAG TCTAATTCCG 60
TTATAAAGCA GACATTTCCG TGGTTATGTA GAAGATGTCG ACCGATCAGA TGAAGCGATC 120
CGCGTCAGGT GGTATCCGAT GTCTTTTGTG ACCATCCAGC CGGTGGTCTT GGCAGCCGCG 180
ACGGGGGACT TGCCGACGAT CGGTACCGCC GTGAGTGCTC GGAACACAGC CGTCTGTGCC 240
CCGACGACGG GGGTGTTACC CCCTGCTGCC AATGACGTGT CGGTCCTGAC GGCGGCCCGG 300
TTCACCGCGC ACACCAAGCA CTACCGAGTG GTGAGTAAGC CGGCCGCGCT GGTCCATGGC 360
ATGTTCGTGG CCCTCCCGGC GGCCACCGCC GATGCGTATG CGACCACCGA GGCCGTCAAT 420
GTGGTCGCGA CCGGTTAAG 439
(2) INFORMATION FOR SEQ ID NO:140:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 1441 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: cDNA
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:140:
GAGGTTGCTG GCAATGGATT TCGGGCTTTT ACCTCCGGAA GTGAATTCAA GCCGAATGTA 60
TTCCGGTCCG GGGCCGGAGT CGATGCTAGC CGCCGCGGCC GCCTGGGACG GTGTGGCCGC 120
GGAGTTGACT TCCGCCGCGG TCTCGTATGG ATCGGTGGTG TCGACGCTGA TCGTTGAGCC 180
GTGGATGGGG CCGGCGGCGG CCGCGATGGC GGCCGCGGCA ACGCCGTATG TGGGGTGGCT 240
GGCCGCCACG GCGGCGCTGG CGAAGGAGAC GGCCACACAG GCGAGGGCAG CGGCGGAAGC 300
GTTTGGGACG GCGTTCGCGA TGACGGTGCC ACCATCCCTC GTCGCGGCCA ACCGCAGCCG 360
GTTGATGTCG CTGGTCGCGG CGAACATTCT GGGGCAAAAC AGTGCGGCGA TCGCGGCTAC 420
CCAGGCCGAG TATGCCGAAA TGTGGGCCCA AGACGCTGCC GTGATGTACA GCTATGAGGG 480
GGCATCTGCG GCCGCGTCGG CGTTGCCGCC GTTCACTCCA CCCGTGCAAG GCACCGGCCC 540
GGCCGGGCCC GCGGCCGCAG CCGCGGCGAC CCAAGCCGCC GGTGCGGGCG CCGTTGCGGA 600
TGCACAGGCG ACACTGGCCC AGCTGCCCCC GGGGATCCTG AGCGACATTC TGTCCGCATT 660
GGCCGCCAAC GCTGATCCGC TGACATCGGG ACTGTTGGGG ATCGCGTCGA CCCTCAACCC 720
GCAAGTCGGA TCCGCTCAGC CGATAGTGAT CCCCACCCCG ATAGGGGAAT TGGACGTGAT 780
CGCGCTCTAC ATTGCATCCA TCGCGACCGG CAGCATTGCG CTCGCGATCA CGAACACGGC 840
CAGACCCTGG CACATCGGCC TATACGGGAA CGCCGGCGGG CTGGGACCGA CGCAGGGCCA 900
TCCACTGAGT TCGGCGACCG ACGAGCCGGA GCCGCACTGG GGCCCCTTCG GGGGCGCGGC 960
GCCGGTGTCC GCGGGCGTCG GCCACGCAGC ATTAGTCGGA GCGTTGTCGG TGCCGCACAG 1020
CTGGACCACG GCCGCCCCGG AGATCCAGCT CGCCGTTCAG GCAACACCCA CCTTCAGCTC 1080
CAGCGCCGGC GCCGACCCGA CGGCCCTAAA CGGGATGCCG GCAGGCCTGC TCAGCGGGAT 1140
GGCTTTGGCG AGCCTGGCCG CACGCGGCAC GACGGGCGGT GGCGGCACCC GTAGCGGCAC 1200
CAGCACTGAC GGCCAAGAGG ACGGCCGCAA ACCCCCGGTA GTTGTGATTA GAGAGCAGCC 1260
GCCGCCCGGA AACCCCCCGC GGTAAAAGTC CGGCAACCGT TCGTCGCCGC GCGGAAAATG 1320
CCTGGTGAGC GTGGCTATCC GACGGGCCGT TCACACCGCT TGTAGTAGCG TACGGCTATG 1380
GACGACGGTG TCTGGATTCT CGGCGGCTAT CAGAGCGATT TTGCTCGCAA CCTCAGCAAA 1440
G 1441
(2) INFORMATION FOR SEQ ID NO:141:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 99 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: protein
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:141:
Met Ser Phe Val Thr Ile Gln Pro Val Val Leu Ala Ala Ala Thr Gly
1 5 10 15
Asp Leu Pro Thr Ile Gly Thr Ala Val Ser Ala Arg Asn Thr Ala Val
20 25 30
Cys Ala Pro Thr Thr Gly Val Leu Pro Pro Ala Ala Asn Asp Val Ser
35 40 45
Val Leu Thr Ala Ala Arg Phe Thr Ala His Thr Lys His Tyr Arg Val
50 55 60
Val Ser Lys Pro Ala Ala Leu Val His Gly Met Phe Val Ala Leu Pro
65 70 75 80
Ala Ala Thr Ala Asp Ala Tyr Ala Thr Thr Glu Ala Val Asn Val Val
85 90 95
Ala Thr Gly
(2) INFORMATION FOR SEQ ID NO:142:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 423 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: protein
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:142:
Met Asp Phe Gly Leu Leu Pro Pro Glu Val Asn Ser Ser Arg Met Tyr
1 5 10 15
Ser Gly Pro Gly Pro Glu Ser Met Leu Ala Ala Ala Ala Ala Trp Asp
20 25 30
Gly Val Ala Ala Glu Leu Thr Ser Ala Ala Val Ser Tyr Gly Ser Val
35 40 45
Val Ser Thr Leu Ile Val Glu Pro Trp Met Gly Pro Ala Ala Ala Ala
50 55 60
Met Ala Ala Ala Ala Thr Pro Tyr Val Gly Trp Leu Ala Ala Thr Ala
65 70 75 80
Ala Leu Ala Lys Glu Thr Ala Thr Gln Ala Arg Ala Ala Ala Glu Ala
85 90 95
Phe Gly Thr Ala Phe Ala Met Thr Val Pro Pro Ser Leu Val Ala Ala
100 105 110
Asn Arg Ser Arg Leu Met Ser Leu Val Ala Ala Asn Ile Leu Gly Gln
115 120 125
Asn Ser Ala Ala Ile Ala Ala Thr Gln Ala Glu Tyr Ala Glu Met Trp
130 135 140
Ala Gln Asp Ala Ala Val Met Tyr Ser Tyr Glu Gly Ala Ser Ala Ala
145 150 155 160
Ala Ser Ala Leu Pro Pro Phe Thr Pro Pro Val Gln Gly Thr Gly Pro
165 170 175
Ala Gly Pro Ala Ala Ala Ala Ala Ala Thr Gln Ala Ala Gly Ala Gly
180 185 190
Ala Val Ala Asp Ala Gln Ala Thr Leu Ala Gln Leu Pro Pro Gly Ile
195 200 205
Leu Ser Asp Ile Leu Ser Ala Leu Ala Ala Asn Ala Asp Pro Leu Thr
210 215 220
Ser Gly Leu Leu Gly Ile Ala Ser Thr Leu Asn Pro Gln Val Gly Ser
225 230 235 240
Ala Gln Pro Ile Val Ile Pro Thr Pro Ile Gly Glu Leu Asp Val Ile
245 250 255
Ala Leu Tyr Ile Ala Ser Ile Ala Thr Gly Ser Ile Ala Leu Ala Ile
260 265 270
Thr Asn Thr Ala Arg Pro Trp His Ile Gly Leu Tyr Gly Asn Ala Gly
275 280 285
Gly Leu Gly Pro Thr Gln Gly His Pro Leu Ser Ser Ala Thr Asp Glu
290 295 300
Pro Glu Pro His Trp Gly Pro Phe Gly Gly Ala Ala Pro Val Ser Ala
305 310 315 320
Gly Val Gly His Ala Ala Leu Val Gly Ala Leu Ser Val Pro His Ser
325 330 335
Trp Thr Thr Ala Ala Pro Glu Ile Gln Leu Ala Val Gln Ala Thr Pro
340 345 350
Thr Phe Ser Ser Ser Ala Gly Ala Asp Pro Thr Ala Leu Asn Gly Met
355 360 365
Pro Ala Gly Leu Leu Ser Gly Met Ala Leu Ala Ser Leu Ala Ala Arg
370 375 380
Gly Thr Thr Gly Gly Gly Gly Thr Arg Ser Gly Thr Ser Thr Asp Gly
385 390 395 400
Gln Glu Asp Gly Arg Lys Pro Pro Val Val Val Ile Arg Glu Gln Pro
405 410 415
Pro Pro Gly Asn Pro Pro Arg
420
(2) INFORMATION FOR SEQ ID NO:143:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 97 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: protein
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:143:
Met Ser Leu Leu Asp Ala His Ile Pro Gln Leu Val Ala Ser Gln Ser
1 5 10 15
Ala Phe Ala Ala Lys Ala Gly Leu Met Arg His Thr Ile Gly Gln Ala
20 25 30
Glu Gln Ala Ala Met Ser Ala Gln Ala Phe His Gln Gly Glu Ser Ser
35 40 45
Ala Ala Phe Gln Ala Ala His Ala Arg Phe Val Ala Ala Ala Ala Lys
50 55 60
Val Asn Thr Leu Leu Asp Val Ala Gln Ala Asn Leu Gly Glu Ala Ala
65 70 75 80
Gly Thr Tyr Val Ala Ala Asp Ala Ala Ala Ala Ser Thr Tyr Thr Gly
85 90 95
Phe
(2) INFORMATION FOR SEQ ID NO:144:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 99 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: protein
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:144:
Cys Arg Leu Cys Leu Asp Ser His Leu Arg Val Val Ala Leu Pro Ala
1 5 10 15
Gly Gln Pro Gly Arg Leu Val Gln Ala Ile Gly Pro Ala Gln Glu Arg
20 25 30
Asp Val Gly Gln Thr Arg Cys Thr Arg Thr Gly Leu Asp Xaa Val Ser
35 40 45
Ala Leu Thr Ala Ala Gln Phe Ala Ala His Ala Gln Ile Tyr Gln Ala
50 55 60
Val Ser Ala Gln Ala Ala Ala Ile His Glu Met Phe Val Asn Thr Leu
65 70 75 80
Gln Xaa Xaa Ser Gly Ser Tyr Ala Ala Thr Glu Ala Ala Asn Ala Ala
85 90 95
Ala Ala Gly
Claims (29)
- 서열 번호 1, 11, 12, 83, 103-108, 125, 127, 129-137, 139 및 140에 개시된 서열, 이 서열의 상보 서열, 및 서열 번호 1, 11, 12, 83, 103-108, 125, 127, 129-137, 139 및 140에 개시된 서열 또는 이의 상보 서열에 보통의 엄중 조건 하에서 하이브리드화하는 DNA 서열로 구성된 군에서 선택된 DNA 서열이 코딩하는 아미노산 서열을 포함하는, 마이코박테리움 투베르쿨로시스(Micobacterium tuberculosis) 항원의 면역원성 부분, 또는 단지 보존적 치환 및/또는 변형에 있어서만 상이한 상기 항원의 변형체를 포함하는 폴리펩티드.
- 서열 번호 16-33, 109, 126, 138, 141, 142에 개시된 서열 및 이의 변형체로 구성된 군에서 선택된 아미노산 서열을 포함하는, 마이코박테리움 투베르쿨로시스 항원의 면역원성 부분, 또는 단지 보존적 치환 및/또는 변형에 있어서만 상이한 상기 항원의 변형체를 포함하는 폴리펩티드.
- 제1항 또는 제2항에 기재된 폴리펩티드를 코딩하는 뉴클레오티드 서열을 포함하는 DNA 분자.
- 제3항에 기재된 DNA 분자를 포함하는 발현 벡터.
- 제4항에 기재된 발현 벡터로 형질전환시킨 숙주 세포.
- 제5항에 있어서, 이. 콜라이(E. coli), 효모 및 포유류 세포로 구성된 군에서 선택되는 것인 숙주 세포.
- 제1항 또는 제2항에 기재된 1종 이상의 폴리펩티드 및 생리학적 허용 담체를 포함하는 약학 조성물.
- 제3항에 기재된 1종 이상의 DNA 분자 및 생리학적 허용 담체를 포함하는 약학 조성물.
- 서열 번호 2-10, 102, 128에 개시된 서열을 가지는 1종 이상의 DNA 분자 및 생리학적 허용 담체를 포함하는 약학 조성물.
- 제1항 또는 제2항에 기재된 1종 이상의 폴리펩티드 및 비특이적 면역 반응 인핸서를 포함하는 백신.
- 서열 번호 2-10, 102, 128에 개시된 서열, 이 서열들의 상보 서열, 및 서열 번호 2-10, 102, 128에 개시된 서열에 하이브리드화하는 DNA 서열로 구성된 군에서 선택된 DNA 서열이 코딩하는 1종 이상의 폴리펩티드; 및비특이적인 면역반응 인핸서를 포함하는 백신.
- 제10항 또는 제11항에 있어서, 비특이적 면역 반응 인핸서가 면역 증강제(adjuvant)인 백신.
- 제3항에 기재된 1종 이상의 DNA 분자 및 비특이적 면역 반응 인핸서를 포함하는 백신.
- 서열 번호 2-10, 102, 128에 개시된 서열을 가지는 1종 이상의 DNA 분자 및 비특이적 면역 반응 인핸서를 포함하는 백신.
- 제13항 또는 제14항에 있어서, 비특이적 면역 반응 인핸서가 면역 증강제인 백신.
- 제7항 내지 제9항 중 어느 한 항에 기재된 약학 조성물을 환자에게 투여하는 것을 포함하는, 환자의 예방 면역성을 유도하는 방법.
- 제10항 내지 제13항 중 어느 한 항에 기재된 백신을 환자에게 투여하는 것을 포함하는, 환자의 예방 면역성을 유도하는 방법.
- 제1항 또는 제2항에 기재된 폴리펩티드를 2 이상 포함하는 융합 단백질.
- 제1항 또는 제2항에 기재된 폴리펩티드와 공지된 마이코박테리움 투베르쿨로시스 항원을 포함하는 융합 단백질.
- 제18항 또는 제19항에 기재된 융합 단백질과 생리적 허용 담체를 포함하는 약학 조성물.
- 제18항 또는 제19항에 기재된 융합 단백질과 비특이적 면역 반응 인핸서를 포함하는 백신.
- 제21항에 있어서, 비특이적 면역 반응 인핸서가 면역 증강제인 백신.
- 제20항에 기재된 약학 조성물을 환자에게 투여하는 것을 포함하는, 환자의 예방 면역성을 유도하는 방법.
- 제21항 또는 제22항에 기재된 백신을 환자에게 투여하는 것을 포함하는, 환자의 예방 면역성을 유도하는 방법.
- (a) 제1항 또는 제2항에 기재된 1종 이상의 폴리펩티드와 환자의 피부 세포를 접촉시키는 단계; 및(b) 환자의 피부 상의 면역 반응을 검출하고 그로부터 환자의 결핵을 검출하는 단계를 포함하는, 환자의 결핵을 검출하는 방법.
- (a) 서열 번호 2-10, 102, 128에 개시된 서열, 이 서열의 상보 서열, 및 서열 번호 2-10, 102, 128에 개시된 서열에 하이브리드화하는 DNA 서열로 구성된 군에서 선택된 DNA 서열이 코딩하는 1종 이상의 폴리펩티드와 환자의 피부 세포를 접촉시키는 단계; 및(b) 환자의 피부 상의 면역 반응을 검출하고 그로부터 환자의 결핵을 검출하는 단계를 포함하는, 환자의 결핵을 검출하는 방법.
- 제25항 또는 제26항에 있어서, 면역 반응이 경결인 방법.
- (a) 제1항 또는 제2항에 기재된 폴리펩티드; 및(b) 상기 폴리펩티드를 환자의 피부 세포와 접촉시키기에 충분한 장치를 포함하는 진단 키트.
- (a) 서열 번호 2-10, 102, 128에 개시된 서열, 이 서열의 상보 서열, 및 서열 번호 2-10, 102, 128에 개시된 서열에 하이브리드화하는 DNA 서열로 구성된 군에서 선택된 DNA 서열이 코딩하는 폴리펩티드; 및(b) 상기 폴리펩티드를 환자의 피부 세포와 접촉시키기에 충분한 장치를 포함하는 진단 키트.
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| US85938197A | 1997-05-20 | 1997-05-20 | |
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| US09/073,010 | 1998-05-05 | ||
| US09/073,010 US6613881B1 (en) | 1997-05-20 | 1998-05-05 | Compounds for immunotherapy and diagnosis of tuberculosis and methods of their use |
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| KR1020087007618A Division KR100924475B1 (ko) | 1997-05-20 | 1998-05-20 | 결핵의 면역치료 및 진단용 화합물과 이의 사용 방법 |
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| KR1020077003582A KR100909640B1 (ko) | 1997-05-20 | 1998-05-20 | 결핵의 면역치료 및 진단용 화합물과 이의 사용 방법 |
| KR1020067010257A KR100893118B1 (ko) | 1997-05-20 | 1998-05-20 | 결핵의 면역치료 및 진단용 화합물과 이의 사용 방법 |
| KR1020087007618A KR100924475B1 (ko) | 1997-05-20 | 1998-05-20 | 결핵의 면역치료 및 진단용 화합물과 이의 사용 방법 |
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| KR1020077003582A KR100909640B1 (ko) | 1997-05-20 | 1998-05-20 | 결핵의 면역치료 및 진단용 화합물과 이의 사용 방법 |
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| US (1) | US6613881B1 (ko) |
| EP (4) | EP1012293B1 (ko) |
| JP (4) | JP4162155B2 (ko) |
| KR (4) | KR100652513B1 (ko) |
| AT (1) | ATE420180T1 (ko) |
| AU (1) | AU742751B2 (ko) |
| BR (1) | BR9809445A (ko) |
| CA (2) | CA2290774A1 (ko) |
| CZ (2) | CZ303194B6 (ko) |
| DE (1) | DE69840449D1 (ko) |
| DK (1) | DK1012293T3 (ko) |
| ES (1) | ES2321039T3 (ko) |
| HU (1) | HU226520B1 (ko) |
| IL (2) | IL133056A0 (ko) |
| NO (4) | NO324880B1 (ko) |
| NZ (1) | NZ501310A (ko) |
| PL (1) | PL191121B1 (ko) |
| PT (1) | PT1012293E (ko) |
| TR (1) | TR200000115T2 (ko) |
| WO (1) | WO1998053075A2 (ko) |
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| US6458366B1 (en) | 1995-09-01 | 2002-10-01 | Corixa Corporation | Compounds and methods for diagnosis of tuberculosis |
| US6592877B1 (en) * | 1995-09-01 | 2003-07-15 | Corixa Corporation | Compounds and methods for immunotherapy and diagnosis of tuberculosis |
| US6982085B2 (en) | 1997-04-02 | 2006-01-03 | Statens Serum Institut | TB diagnostic based on antigens from M. tuberculosis |
| US7037510B2 (en) | 1997-04-18 | 2006-05-02 | Statens Serum Institut | Hybrids of M. tuberculosis antigens |
| JP4280309B2 (ja) * | 1997-06-06 | 2009-06-17 | ザ リージェンツ オブ ザ ユニバーシティー オブ カリフォルニア | Ｄｎａ免疫刺激配列活性の阻害剤 |
| CA2319380A1 (en) * | 1997-11-10 | 1999-05-20 | Statens Serum Institut | Nucleic acid fragments and polypeptide fragments derived from m. tuberculosis |
| ATE445638T1 (de) | 1998-11-04 | 2009-10-15 | Isis Innovation | Tuberkulose diagnose test |
| US20030027774A1 (en) * | 1999-03-18 | 2003-02-06 | Ronald C. Hendrickson | Tuberculosis antigens and methods of use therefor |
| US8143386B2 (en) * | 1999-04-07 | 2012-03-27 | Corixa Corporation | Fusion proteins of mycobacterium tuberculosis antigens and their uses |
| AU779495B2 (en) * | 1999-07-13 | 2005-01-27 | Statens Serum Institut | Tuberculosis vaccine and diagnostics based on the mycobacterium tuberculosis esat-6 gene family |
| WO2001024820A1 (en) * | 1999-10-07 | 2001-04-12 | Corixa Corporation | Fusion proteins of mycobacterium tuberculosis |
| US6316205B1 (en) | 2000-01-28 | 2001-11-13 | Genelabs Diagnostics Pte Ltd. | Assay devices and methods of analyte detection |
| WO2001062893A2 (en) | 2000-02-25 | 2001-08-30 | Corixa Corporation | Compounds and methods for diagnosis and immunotherapy of tuberculosis |
| WO2001079274A2 (en) * | 2000-04-19 | 2001-10-25 | Statens Serum Institut | Tuberculosis antigens and methods of use thereof |
| PT1542732E (pt) * | 2000-06-20 | 2009-11-06 | Corixa Corp | Proteínas de fusão de mycobacterium tuberculosis |
| US7026465B2 (en) * | 2002-02-15 | 2006-04-11 | Corixa Corporation | Fusion proteins of Mycobacterium tuberculosis |
| US7482116B2 (en) | 2002-06-07 | 2009-01-27 | Dna Genotek Inc. | Compositions and methods for obtaining nucleic acids from sputum |
| US20050164168A1 (en) * | 2003-03-28 | 2005-07-28 | Cullum Malford E. | Method for the rapid diagnosis of infectious disease by detection and quantitation of microorganism induced cytokines |
| US8475735B2 (en) * | 2004-11-01 | 2013-07-02 | Uma Mahesh Babu | Disposable immunodiagnostic test system |
| CN101090974B (zh) | 2004-11-16 | 2011-05-11 | 克鲁塞尔荷兰公司 | 包含重组病毒载体的多价疫苗 |
| CA2606962A1 (en) | 2005-04-29 | 2006-11-09 | Fusion Antibodies Limited | Assays for diagnosis of tuberculosis and uses thereof |
| ATE530569T1 (de) | 2005-07-01 | 2011-11-15 | Forsyth Dental In Ry For Children Fa | Assays zum nachweis von tuberkulose- antigenen, und impfstoffe |
| US20070081944A1 (en) * | 2005-09-30 | 2007-04-12 | Reed Steven G | Iontophoresis apparatus and method for the diagnosis of tuberculosis |
| CA2649688A1 (en) | 2006-03-14 | 2007-09-20 | Oregon Health & Science University | Methods for detecting a mycobacterium tuberculosis infection |
| KR20110044883A (ko) * | 2008-07-25 | 2011-05-02 | 글락소스미스클라인 바이오로지칼즈 에스.에이. | 신규한 조성물 및 방법 |
| ES2647321T3 (es) | 2008-07-25 | 2017-12-20 | Glaxosmithkline Biologicals S.A. | Composiciones y procedimientos novedosos |
| PL2315834T3 (pl) | 2008-07-25 | 2018-12-31 | Glaxosmithkline Biologicals S.A. | Białko rv2386c związane z gruźlicą, jego kompozycje i zastosowania |
| MY156697A (en) | 2010-01-27 | 2016-03-15 | Glaxosmithkline Biolog Sa | Modified tuberculosis antigens |
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| WO2016130543A1 (en) | 2015-02-09 | 2016-08-18 | Abogen, Inc. | Devices, solutions and methods for sample collection related applications, analysis and diagnosis |
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1998
- 1998-05-05 US US09/073,010 patent/US6613881B1/en not_active Expired - Fee Related
- 1998-05-20 DE DE69840449T patent/DE69840449D1/de not_active Expired - Lifetime
- 1998-05-20 EP EP98924827A patent/EP1012293B1/en not_active Expired - Lifetime
- 1998-05-20 JP JP55063498A patent/JP4162155B2/ja not_active Expired - Fee Related
- 1998-05-20 TR TR2000/00115T patent/TR200000115T2/xx unknown
- 1998-05-20 EP EP08172265A patent/EP2172551A3/en not_active Withdrawn
- 1998-05-20 CZ CZ20080478A patent/CZ303194B6/cs not_active IP Right Cessation
- 1998-05-20 IL IL13305698A patent/IL133056A0/xx unknown
- 1998-05-20 PT PT98924827T patent/PT1012293E/pt unknown
- 1998-05-20 WO PCT/US1998/010407 patent/WO1998053075A2/en active Application Filing
- 1998-05-20 PL PL337330A patent/PL191121B1/pl not_active IP Right Cessation
- 1998-05-20 DK DK98924827T patent/DK1012293T3/da active
- 1998-05-20 CZ CZ0410099A patent/CZ300866B6/cs not_active IP Right Cessation
- 1998-05-20 KR KR1019997010775A patent/KR100652513B1/ko not_active IP Right Cessation
- 1998-05-20 ES ES98924827T patent/ES2321039T3/es not_active Expired - Lifetime
- 1998-05-20 EP EP10174426.6A patent/EP2270170B1/en not_active Expired - Lifetime
- 1998-05-20 CA CA002290774A patent/CA2290774A1/en not_active Abandoned
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- 1998-05-20 BR BR9809445-9A patent/BR9809445A/pt not_active Application Discontinuation
- 1998-05-20 AU AU76907/98A patent/AU742751B2/en not_active Ceased
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- 1998-05-20 KR KR1020087007618A patent/KR100924475B1/ko not_active IP Right Cessation
- 1998-05-20 AT AT98924827T patent/ATE420180T1/de active
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2007
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