Madden D R
Biophysics Department, Max-Planck-Institute for Medical Research, Heidelberg, Germany.
Annu Rev Immunol. 1995;13:587-622. doi: 10.1146/annurev.iy.13.040195.003103.
The ability of MHC molecules to present a broad spectrum of peptide antigens for T cell recognition requires a compromise between high affinity and broad specificity. Three-dimensional atomic structures of several class I and class II MHC molecules reveal a unique structural solution to this problem: Tight binding to the peptide main chain is supplemented by more or less restrictive interactions with peptide side chains. In spite of these contacts, peptide side-chain and conformational variability ensures that the resulting peptide-MHC complex presents an antigenically unique surface to T cell receptors. Extension of this understanding to other peptide-MHC complexes, including agonist/antagonist peptides and the identification of antigenic peptides within protein sequences, however, requires a detailed analysis of the interactions that determine both peptide-MHC binding affinity and the conformations of bound peptides. While many of these interactions can be modeled by homology with known structures, their specificity can depend sensitively on subtle and long-range structural effects. Structurally and immunologically important distinctions are also found between the class I and class II peptide-binding strategies. Taken together, these interactions ultimately determine the ability of an individual to respond successfully to immune challenges.
MHC分子呈现广泛肽抗原以供T细胞识别的能力，需要在高亲和力和广泛特异性之间做出妥协。几种I类和II类MHC分子的三维原子结构揭示了针对此问题的独特结构解决方案：与肽主链的紧密结合通过与肽侧链或多或少的限制性相互作用得到补充。尽管存在这些相互作用，但肽侧链和构象变异性确保了所得肽-MHC复合物向T细胞受体呈现抗原性独特的表面。然而，将这种理解扩展到其他肽-MHC复合物，包括激动剂/拮抗剂肽以及蛋白质序列中抗原肽的鉴定，需要详细分析决定肽-MHC结合亲和力和结合肽构象的相互作用。虽然其中许多相互作用可以通过与已知结构的同源性进行建模，但其特异性可能敏感地取决于微妙和远程的结构效应。在I类和II类肽结合策略之间也发现了结构和免疫学上的重要区别。综合起来，这些相互作用最终决定了个体成功应对免疫挑战的能力。
