SIGNIFICANCE OF THE 6 PEPTIDE-BINDING POCKETS OF HLA-A2.1 IN INFLUENZA-A MATRIX PEPTIDE-SPECIFIC CYTOTOXIC T-LYMPHOCYTE REACTIVITY

SIGNIFICANCE OF THE 6 PEPTIDE-BINDING POCKETS OF HLA-A2.1 IN INFLUENZA-A MATRIX PEPTIDE-SPECIFIC CYTOTOXIC T-LYMPHOCYTE REACTIVITY
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DOI:
10.1016/0198-8859(94)90010-8
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发表时间:
1994-10-01
期刊:
影响因子:
2.7
通讯作者:
FRELINGER, JA
FRELINGER, JA
中科院分区:
医学4区
文献类型:
--
作者:
MATSUI, M;MOOTS, RJ;FRELINGER, JA

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为了评估HLA-A2.1的六个肽结合口袋在FMP特异性CTL识别中的作用,我们构建了一个广泛的HMy2.C1R细胞系文库,该细胞系表达在六个口袋中的每一个中具有不同氨基酸取代的突变HLA-A2.1分子。测试这些细胞系将合成的FMP 58-66呈递给FMP特异性HLA-A2的能力。1-限制性人CTL系。在12个突变体中,有6个突变体的口袋B的氨基酸改变显著影响了FMP特异性CTL的识别,表明口袋B在FMP特异性CTL识别中起着关键作用。令人惊讶的是,除了口袋F之外,所有其他口袋中的突变也对CTL识别具有显著影响。这些结果表明,即使是浅口袋,这可能是不太重要的肽结合比深口袋,在FMP特异性CTL识别中发挥了至关重要的作用。
To evaluate the roles of the six peptide-binding pockets of HLA-A2.1 in FMP-specific CTL recognition, we have constructed an extensive library of HMy2.C1R cell lines expressing mutant HLA-A2.1 molecules with different amino acid substitutions in each of the six pockets. These cell lines were tested for their ability to present synthetic FMP 58-66 to FMP-specific, HLA-A2. 1-restricted human CTL lines. Six of 12 mutants with amino acid changes in pocket B significantly affect the FMP-specific CTL recognition, suggesting that pocket B plays a critical role in FMP-specific CTL recognition. Surprisingly, mutations in all other pockets, except for pocket F, also have significant effects on the CTL recognition. These results suggest that even the shallow pockets, which are likely to be less critical for peptide binding than the deep pockets, play a crucial role in FMP-specific CTL recognition.