Utz U, Koenig S, Coligan J E, Biddison W E
Molecular Immunology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health (NIH), Bethesda, MD 20892.
J Immunol. 1992 Jul 1;149(1):214-21.
To determine whether similar or dissimilar molecular features of class I molecules are involved in the presentation of structurally distinct peptides, we have investigated the influence of different pockets of the HLA-A2.1 molecule on the presentation of three different viral peptides. HTLV-I Tax peptide 12-19, HCMV gB 619-628, and influenza M1 58-66 are minimal peptides that induce HLA-A2.1-restricted noncross-reactive CTL. A detailed analysis of the structural features of HLA-A2.1 that are involved in peptide presentation was undertaken using a panel of 11 HLA-A2 mutants with single amino acid substitutions within pockets present in the peptide binding site. Nine of the 11 mutants affected presentation of each of the three peptides, whereas the other two mutants had negative effects on presentation of only two of these viral peptides. These results indicate that common structural features in HLA-A2 determine the binding of different peptides, and help to provide a plausible explanation for how structurally diverse peptides bind to HLA-A2.
为了确定I类分子的相似或不同分子特征是否参与结构不同的肽的呈递，我们研究了HLA-A2.1分子的不同口袋对三种不同病毒肽呈递的影响。HTLV-I Tax肽12-19、HCMV gB 619-628和流感M1 58-66是诱导HLA-A2.1限制性非交叉反应性CTL的最小肽。使用一组11个HLA-A2突变体进行了详细分析，这些突变体在肽结合位点的口袋内具有单个氨基酸取代，以研究参与肽呈递的HLA-A2.1的结构特征。11个突变体中的9个影响了这三种肽中每种肽的呈递，而其他两个突变体仅对其中两种病毒肽的呈递有负面影响。这些结果表明，HLA-A2中的共同结构特征决定了不同肽的结合，并有助于为结构多样的肽如何结合到HLA-A2提供一个合理的解释。
