HLA-A*0201 与 Melan-A/MART-1(26(27L)-35) 肽模拟物复合物的晶体结构揭示了构象异质性，并突出了 T 细胞识别的简并性。
Crystal structures of HLA-A*0201 complexed with Melan-A/MART-1(26(27L)-35) peptidomimetics reveal conformational heterogeneity and highlight degeneracy of T cell recognition.
机构信息
Institut des Sciences Moléculaires (UMR-CNRS 5255) and Institut Européen de Chimie et Biologie (IECB), Université de Bordeaux, 2 Rue Robert Escarpit, 33607 Pessac, France.
出版信息
J Med Chem. 2010 Oct 14;53(19):7061-6. doi: 10.1021/jm100683p.
Abstract
There is growing interest in using tumor associated antigens presented by class I major histocompatibility complex (MHC-I) proteins as cancer vaccines. As native peptides are poorly stable in biological fluids, researchers have sought to engineer synthetic peptidomimetics with greater biostability. Here, we demonstrate that antigenic peptidomimetics of the Melan-A/MART-1(26(27L)-35) melanoma antigen adopt strikingly different conformations when bound to MHC-I, highlighting the degeneracy of T cell recognition and revealing the challenges associated with mimicking native peptide conformation.
摘要
人们对使用 I 类主要组织相容性复合体 (MHC-I) 蛋白呈递的肿瘤相关抗原作为癌症疫苗越来越感兴趣。由于天然肽在生物流体中稳定性较差，研究人员一直在寻求工程合成具有更高生物稳定性的肽模拟物。在这里，我们证明了黑色素瘤抗原 Melan-A/MART-1(26(27L)-35)的抗原肽模拟物与 MHC-I 结合时采用截然不同的构象，突出了 T 细胞识别的简并性，并揭示了模拟天然肽构象所面临的挑战。
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