The seminal discovery in the early 1970s, credited to Peter Doherty and Rolf Zinkernagel, of major histocompatibility complex (MHC) restriction exhibited by cytotoxic T cells represented a major conceptual advance in understanding antigen recognition by conventional T cells. This advance also led to other major new insights into the ontogeny and immunobiology of T cells and catalyzed a renaissance in viral immunology. In this commentary in honor of Peter Doherty, I offer five brief reflections on different aspects of the phenomenon of MHC restriction and the process by which it was discovered and explained. In the first of these sections, I offer a reinterpretation of MHC restriction that reframes the constraints on self-MHC recognition in terms of the probabilities of recognizing a given nominal antigen peptide in the context of an MHC molecule that is nonself on the basis of differing in amino acid sequence from the self-restriction element at one or more positions. Subsequent sections address: (i) the ways in which general ideas, developed subsequent to the discovery of MHC restriction, about the intricacies of antigen recognition by antibodies apply to T cell receptors binding to MHC/peptide complexes; (ii) how to reconcile the existence of MHC restriction with the impressive magnitude of T cell responses to nonself MHC antigens; (iii) the possible relevance to MHC restriction and immune system function of ideas from mathematical logic that relate to the consequences of self-reference; and (iv) the implications for the philosophy of science of MHC restriction and the processes of its discovery and acceptance within the immunology research community.

中文翻译：

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五项法案中关于MHC限制和T细胞识别的研究。

归因于Peter Doherty和Rolf Zinkernagel于1970年代初期对细胞毒性T细胞所表现出的主要组织相容性复合物（MHC）的限制，这一开创性发现代表了理解传统T细胞对抗原的认识方面的重要概念进展。这项进展还导致了对T细胞的发生和免疫生物学的其他重大新见解，并促进了病毒免疫学的复兴。在纪念彼得·多赫蒂（Peter Doherty）的这篇评论中，我对MHC限制现象的不同方面及其发现和解释过程进行了五点简要思考。在这些部分的第一部分，我提供了对MHC限制的重新解释，它根据在自身以外的氨基酸序列不同的非MHC分子的背景下识别给定标称抗原肽的可能性，重新构造了对自身MHC识别的限制-一个或多个位置的限制元素。后续章节讨论：（i）在发现MHC限制后，关于抗体识别抗原的复杂性的一般性思想如何应用于结合MHC /肽复合物的T细胞受体的方式；（ii）如何将MHC限制的存在与T细胞对非自身MHC抗原的令人印象深刻的反应相协调；（iii）与自我参照的后果有关的数学逻辑思想与MHC限制和免疫系统功能的可能关联性；（iv）限制MHC的科学原理及其在免疫学研究界的发现和接受过程。