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Major Histocompatibility Complex Class I Ligands of Rhesus Macaques NK Cell Receptors
Major Histocompatibility Complex Class I Ligands of Rhesus Macaques NK Cell Receptors
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20260202105135
- ISBN
- 9798291587904
- DDC
- 616.079
- 서명/저자
- Major Histocompatibility Complex Class I Ligands of Rhesus Macaques NK Cell Receptors
- 발행사항
- [Sl] : The University of Wisconsin - Madison, 2025
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2025
- 형태사항
- 167 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 87-03, Section: B.
- 주기사항
- Advisor: Evans, David T.
- 학위논문주기
- Thesis (Ph.D.)--The University of Wisconsin - Madison, 2025.
- 초록/해제
- 요약Major Histocompatibility Complex (MHC) class I molecules play a crucial role in immune surveillance and contribute substantially to varying levels of resistance to many infectious diseases. MHC class I molecules are expressed on all nucleated cells and serve as ligands for NK cell receptors such as killer cell immunoglobulin-like receptors (KIR) and CD94/NKG2 heterodimeric receptors. Macaques are an important translational research model, but have undergone divergent evolution in many immunogenetic regions of their genome. Macaques have an expanded array of MHC-A and MHC-B genes along with an increased complement of lineage II KIR and NKG2C receptors. This has substantially limited our ability to fully understand regulation of NK cells and comparative immunology in this important pre-clinical model. To provide a more complete foundation for studying NK cell biology, I have conducted a detailed study of rhesus macaque MHC class I molecules and their NK cell receptors. I identified MHC class I ligands for 12 rhesus macaque KIRs of previously unknown specificity that fell into three general categories: interactions with multiple Mamu-Bw4 molecules, interactions with Mamu-AG, or interactions with Mamu-A1*012:01. These findings support overlapping, but nonredundant, patterns of MHC class I ligand recognition that reflects extensive functional diversification of rhesus macaque KIR. Additionally, I showed that N-linked glycosylation at specific sites in the D0 domain of rhesus KIR molecules play a role in modulating surface expression and contribute to ligand specificity. Finally, I established that Mamu-E allotypes are differentially stabilized by polymorphic MHC class I leader-derived peptides and that CD94/NKG2 recognition and response is Mamu-E/peptide-dependent. This study suggests that availability of specific leader peptides for presentation by Mamu-E could lower the threshold for NK cell activation by decreasing or interrupting inhibitory signaling. This dissertation serves as a valuable resource for immunologists providing new insights into NK cell responses in rhesus macaques as a pre-clinical model. It lays the foundation for further characterization on how MHC class I peptide presentation modulates NK cell responses and can help discern the intricacies of innate immune responses to infectious disease.
- 일반주제명
- Immunology
- 일반주제명
- Cellular biology
- 일반주제명
- Pathology
- 일반주제명
- Molecular biology
- 키워드
- Rhesus macaque
- 기타저자
- The University of Wisconsin - Madison Cellular & Molecular Pathology
- 기본자료저록
- Dissertations Abstracts International. 87-03B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■006m o d
■007cr#unu||||||||
■020 ▼a9798291587904
■035 ▼a(MiAaPQ)AAI32239649
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a616.079
■1001 ▼aAnderson, Jennifer Lynn.
■24510▼aMajor Histocompatibility Complex Class I Ligands of Rhesus Macaques NK Cell Receptors
■260 ▼a[Sl]▼bThe University of Wisconsin - Madison▼c2025
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2025
■300 ▼a167 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 87-03, Section: B.
■500 ▼aAdvisor: Evans, David T.
■5021 ▼aThesis (Ph.D.)--The University of Wisconsin - Madison, 2025.
■520 ▼aMajor Histocompatibility Complex (MHC) class I molecules play a crucial role in immune surveillance and contribute substantially to varying levels of resistance to many infectious diseases. MHC class I molecules are expressed on all nucleated cells and serve as ligands for NK cell receptors such as killer cell immunoglobulin-like receptors (KIR) and CD94/NKG2 heterodimeric receptors. Macaques are an important translational research model, but have undergone divergent evolution in many immunogenetic regions of their genome. Macaques have an expanded array of MHC-A and MHC-B genes along with an increased complement of lineage II KIR and NKG2C receptors. This has substantially limited our ability to fully understand regulation of NK cells and comparative immunology in this important pre-clinical model. To provide a more complete foundation for studying NK cell biology, I have conducted a detailed study of rhesus macaque MHC class I molecules and their NK cell receptors. I identified MHC class I ligands for 12 rhesus macaque KIRs of previously unknown specificity that fell into three general categories: interactions with multiple Mamu-Bw4 molecules, interactions with Mamu-AG, or interactions with Mamu-A1*012:01. These findings support overlapping, but nonredundant, patterns of MHC class I ligand recognition that reflects extensive functional diversification of rhesus macaque KIR. Additionally, I showed that N-linked glycosylation at specific sites in the D0 domain of rhesus KIR molecules play a role in modulating surface expression and contribute to ligand specificity. Finally, I established that Mamu-E allotypes are differentially stabilized by polymorphic MHC class I leader-derived peptides and that CD94/NKG2 recognition and response is Mamu-E/peptide-dependent. This study suggests that availability of specific leader peptides for presentation by Mamu-E could lower the threshold for NK cell activation by decreasing or interrupting inhibitory signaling. This dissertation serves as a valuable resource for immunologists providing new insights into NK cell responses in rhesus macaques as a pre-clinical model. It lays the foundation for further characterization on how MHC class I peptide presentation modulates NK cell responses and can help discern the intricacies of innate immune responses to infectious disease.
■590 ▼aSchool code: 0262.
■650 4▼aImmunology
■650 4▼aCellular biology
■650 4▼aPathology
■650 4▼aMolecular biology
■653 ▼aLigand recognition
■653 ▼aRhesus macaque
■653 ▼aMajor Histocompatibility Complex
■653 ▼aImmune surveillance
■690 ▼a0982
■690 ▼a0379
■690 ▼a0307
■690 ▼a0571
■71020▼aThe University of Wisconsin - Madison▼bCellular & Molecular Pathology.
■7730 ▼tDissertations Abstracts International▼g87-03B.
■790 ▼a0262
■791 ▼aPh.D.
■792 ▼a2025
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17359542▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
