T cell activity correlates with oligomeric peptide-major histocompatibility complex binding on T cell surface
T cell activity correlates with oligomeric peptide-major histocompatibility complex binding on T cell surface
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DOI：
10.1074/jbc.m109231200
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发表时间：
2001-12-14
影响因子：
4.8
通讯作者：
Collins, EJ
中科院分区：
文献类型：
--
作者：
Buslepp, J;Zhao, R;Collins, EJ
CD 8（+）T细胞识别病毒感染的细胞需要区分自身和非自身的I类主要组织相容性复合物（pMHC）。宿主T细胞对外源pMHC的识别是同种异体或异种器官移植排斥反应的主要因素。AHIII 12.2是识别异种（人）I类NMC HLA-A2.1分子（A2）和同基因鼠I类MHC H-2 D-b分子（D-b）的鼠T细胞克隆。A2和D-b的识别都是肽依赖性的，并且已确定所识别的肽的序列。与A2结合的抗原肽的改变导致AHIII 12.2 T细胞应答性的巨大变化。与A2结合的三种代表性肽（激动剂、无效和拮抗剂）的晶体结构部分解释了AHIII 12.2反应性的变化。使用I类pMHC八聚体，在T细胞活性和pMHC复合物对T细胞受体的亲和力之间观察到强相关性。然而，与以前的研究相反，我们看到与AHIII12.2细胞表面结合的pMHC多聚体的半衰期相似。
Recognition of virally infected cells by CD8(+) T cells requires differentiation between self and nonself peptide-class I major histocompatibility complexes (pMHC). Recognition of foreign pMHC by host T cells is a major factor in the rejection of transplanted organs from the same species (allotransplant) or different species (xenotransplant). AHIII12.2 is a murine T cell clone that recognizes the xenogeneic (human) class I NMC HLA-A2.1 molecule (A2) and the syngeneic murine class I MHC H-2 D-b molecule (D-b). Recognition of both A2 and D-b are peptide-dependent, and the sequences of the peptides recognized have been determined. Alterations in the antigenic peptides bound to A2 cause large changes in AHIII12.2 T cell responsiveness. Crystal structures of three representative peptides (agonist, null, and antagonist) bound to A2 partially explain the changes in AHIII12.2 responsiveness. Using class I pMHC octamers, a strong correlation is seen between T cell activity and the affinity of pMHC complexes for the T cell receptor. However, contrary to previous studies, we see similar half-lives for the pMHC multimers bound to the AHIII12.2 cell surface.