Ogasawara K, Maloy W L, Schwartz R H
Nature. 1987;325(6103):450-2. doi: 10.1038/325450a0.
The ability of an animal to respond to a given antigenic peptide depends on its major histocompatibility complex (MHC) type. Some peptides are not immunogenic when combined with a particular form of the MHC-encoded molecule. This non-responsiveness is regulated by immune response (Ir) genes and is thought to arise by one of two distinct mechanisms. Either the MHC-encoded molecules physically fail to interact with the antigen, preventing the activation of T cells with appropriate receptors, or they limit the expressed repertoire of T cell clones so that no T cells are available to be activated by existing complexes of MHC-encoded molecules and antigen. Experimental evidence has been generated to support both mechanisms. However, the relative importance of each has not been clearly established. In this study we started with a peptide that was immunogenic in B10 mice; it was thus known to be able to interact with the MHC molecule, and T cells existed which could recognise the peptide-MHC complex. Based on previous experiments, we then changed only those parts of the peptide that we thought interacted with the T-cell receptor. All the new analogues created were still immunogenic, confirming that the amino-acid substitutions that we had made did not prevent productive interactions with the MHC-encoded molecule. No limitations ('holes') in the T-cell repertoire were found. The experiments demonstrate the vast potential of the T-cell population to recognize many different analogues, each in a unique way, and suggest that constraints on the diversity of the T-cell repertoire may not be a major explanation for Ir gene defects.
动物对特定抗原肽作出反应的能力取决于其主要组织相容性复合体（MHC）类型。某些肽与特定形式的MHC编码分子结合时不具有免疫原性。这种无反应性由免疫反应（Ir）基因调控，被认为是由两种不同机制之一引起的。要么MHC编码分子实际上无法与抗原相互作用，从而阻止具有适当受体的T细胞被激活，要么它们限制了T细胞克隆的表达库，以至于没有T细胞可被现有的MHC编码分子与抗原的复合物激活。已经产生了实验证据来支持这两种机制。然而，每种机制的相对重要性尚未明确确定。在本研究中，我们从一种在B10小鼠中具有免疫原性的肽开始；因此已知它能够与MHC分子相互作用，并且存在能够识别肽-MHC复合物的T细胞。基于先前的实验，我们随后仅改变了我们认为与T细胞受体相互作用的肽的那些部分。所产生的所有新类似物仍然具有免疫原性，这证实了我们所做的氨基酸替换并没有阻止与MHC编码分子的有效相互作用。未发现T细胞库中的限制（“漏洞”）。这些实验证明了T细胞群体识别许多不同类似物的巨大潜力，每种类似物都以独特的方式被识别，并表明对T细胞库多样性的限制可能不是Ir基因缺陷的主要解释。
