首页> 美国卫生研究院文献>Proceedings of the National Academy of Sciences of the United States of America >An optimal viral peptide recognized by CD8+ T cells binds very tightly to the restricting class I major histocompatibility complex protein on intact cells but not to the purified class I protein.
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An optimal viral peptide recognized by CD8+ T cells binds very tightly to the restricting class I major histocompatibility complex protein on intact cells but not to the purified class I protein.

机译:CD8 + T细胞识别的最佳病毒肽与完整细胞上的限制性I类主要组织相容性复合蛋白紧密结合但不与纯化的I类蛋白紧密结合。

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摘要

CD8+ cytotoxic T lymphocytes recognize cell surface complexes formed by class I major histocompatibility complex (MHC-I) glycoproteins and antigenic peptides. We have identified a peptide nonamer (termed IV9) derived from the human immunodeficiency virus that is over a millionfold more active (at subpicomolar concentrations) than peptide analogues longer or shorter by one or two amino acid residues. Although IV9 does not detectably bind to isolated MHC-I molecules as measured by equilibrium dialysis, we quantitated its specific binding in unaltered form to MHC-I on intact cells. Less than 1% of cell surface MHC-I forms complexes with IV9, which suffices to trigger maximal cytotoxic T-lymphocyte activity. By contrast, a peptide dodecamer that includes the IV9 sequence and is active at micromolar concentrations does not bind to MHC-I on intact cells, raising the possibility that this longer peptide undergoes processing. Using stoichiometrically iodinated IV9 to obviate the ambiguities associated with trace labeling methods, we measured the dissociation kinetics of purified peptide/MHC-I complexes isolated by affinity chromatography and found these complexes to be exceedingly stable (t1/2 = 200-600 hr).
机译:CD8 +细胞毒性T淋巴细胞识别由I类主要组织相容性复合物(MHC-1)糖蛋白和抗原性肽形成的细胞表面复合物。我们已经鉴定出一种源自人免疫缺陷病毒的肽九聚体(称为IV9),其活性(在皮摩尔浓度下)比更长或更短一个或两个氨基酸残基的肽类似物高一百万倍。尽管通过平衡透析测量,IV9不能检测到与分离的MHC-1分子的结合,但我们以完整的形式定量了其与完整细胞上MHC-1的特异性结合。少于1%的细胞表面MHC-1与IV9形成复合物,足以触发最大的细胞毒性T淋巴细胞活性。相反,包括IV9序列并且在微摩尔浓度下有活性的十二肽肽不与完整细胞上的MHC-1结合,从而增加了这种较长肽进行加工的可能性。使用化学计量碘化的IV9消除了与痕量标记方法相关的歧义,我们测量了通过亲和色谱分离的纯化肽/ MHC-1复合物的解离动力学,发现这些复合物极其稳定(t1 / 2 = 200-600 hr)。

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