Restoration of CTL recognition of a mutant FMP peptide by a compensatory change in HLA-A2.
Restoration of CTL recognition of a mutant FMP peptide by a compensatory change in HLA-A2.
复制标题
通过 HLA-A2 的补偿性变化恢复 CTL 对突变 FMP 肽的识别。
DOI：
10.1007/bf00163966
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发表时间：
1994
期刊：
影响因子：
3.2
通讯作者：
Frelinger,JA
中科院分区：
文献类型：
--
作者：
Matsui,M;Frelinger,JA
主要组织相容性复合体的I类分子对于CD 8+细胞毒性T淋巴细胞（CTL）的抗原特异性识别是必需的。这些分子结合与内质网中的β 2-微球蛋白相关的加工肽，通过高尔基复合体将它们转运到细胞表面，并将它们呈递给CTL（汤森and Bodmer 1989;汤森et al.1989;汤森et al.1990）。晶体学分析揭示了在I类分子HLA-A2的肽结合沟内的六个口袋，称为口袋AF。1（Saper等人，1991）。在HLA-Aw 68（加勒特等，1989; Guo等，1992）、HLA-B27（Madden等，1991; Colbert等，1993）和H-2K B（Matsumura等，1992）中也观察到类似的结构。这些口袋在CTL识别中起关键作用。最近，天然肽与HLA-A2。1分离并测序（Falk等1991; Hunt等1992; Wei和克雷斯韦尔1992）。这些数据表明，HLA-A2相关肽通常在位置2（P2）具有亮氨酸或甲硫氨酸，这表明P2是HLA-A2相关肽在肽结合沟中结合和定位的锚残基。因为P2被认为与口袋B相互作用并适合口袋B（Falk等1991; Latron等1991; Madden等1991; Guo等1992; Matsumura等1992; Colbert等1993），所以认为该口袋对于肽结合以及因此对于CTL识别是重要的。在这项研究中，我们研究了甲型流感病毒基质肽（FMP 58-66）的P2和HLA-A2的口袋B中的氨基酸残基之间的相互作用。1在FMP特异性CTL识别中，使用在P2和HLAA 2处具有单个氨基酸取代的FMP 58-66的肽类似物。1的突变体，在口袋B中具有单个氨基酸变化。人MMP特异性ttLA-A2。1-从健康HLA-A2产生限制性CTL系（BC）。1阳性
Class I molecules of the major histocompatibility complex are essential for antigen-specific recognition by CD8+ cytotoxic T lymphocytes (CTL). These molecules bind processed peptides in association with] 32-microglobulin in the endoplasmic reticulum, transport them via the Golgi complex to the cell surface, and present them to CTL (Townsend and Bodmer 1989; Townsend et al. 1989; Townsend et al. 1990). Crystallographic analysis has revealed six pockets, designated as pockets AF, within a peptide-binding groove of the class I molecule HLA-A2. 1 (Saper et al. 1991). Similar structures are seen in HLA-Aw68 (Garrett et al. 1989; Guo et al. 1992), HLA-B27 (Madden et al. 1991; Colbert et al. 1993), and H-2K b (Matsumura et al. 1992). These pockets play a critical role in CTL recognition. Recently, natural peptides associated with HLA-A2. 1 were isolated and sequenced (Falk et al. 1991; Hunt et al. 1992; Wei and Cresswell 1992). These data have indicated that HLA-A2-associated peptides commonly possess leucine or methionine at position 2 (P2), suggesting that P2 is an anchor residue for binding and positioning of HLA-A2-associated peptides in the peptidebinding groove. Because P2 is thought to interact with, and fit into, pocket B (Falk et al. 1991; Latron et al. 1991; Madden et al. 1991; Guo et al. 1992; Matsumura et al. 1992; Colbert et al. 1993), this pocket is believed to be important for peptide binding and, therefore, CTL recognition. In this study, we have examined interaction between P2 of influenza A matrix peptide (FMP 58-66) and amino acid residues in pocket B of HLA-A2. 1 in FMP-specific CTL recognition, using peptide analogues of FMP 58-66 with single amino acid substitutions at P2 and HLAA2. 1 mutants with single amino acid changes in pocket B. A human FMP-specific, ttLA-A2. 1-restricted CTL line (BC) was generated from a healthy HLA-A2. 1-positive