Cohn Melvin
Conceptual Immunology Group, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Mol Immunol. 2005 Aug;42(12):1419-43. doi: 10.1016/j.molimm.2005.01.013. Epub 2005 Feb 26.
Given that the recognition of the allele-specific determinants expressed by MHC-encoded restricting elements (R) is germline encoded and selected, whereas the recognition of peptide (P) is somatically encoded and selected, then two different combining sites must be under selection. This necessitates a multirecognitive-single T-cell antigen-receptor (TCR) with anti-R and anti-P paratopes that function in concert to signal restrictive reactivity. The consequences of this "two repertoire" postulate not only gives us a concept of TCR structure quite distinct from that at present generally accepted, but, in addition, resolves many existent contradictions. The problems of the positive and negative selection, alloreactivity, Self-Nonself (S-NS) discrimination, the nature and size of the repertoire, and the related experimental interpretations, are discussed. Further the Tritope Model is compared with previously proposed models to justify why a competing model is warranted.
鉴于对由主要组织相容性复合体（MHC）编码的限制性元件（R）所表达的等位基因特异性决定簇的识别是由种系编码并经过选择的，而对肽段（P）的识别是由体细胞编码并经过选择的，那么两个不同的结合位点必定处于选择之下。这就需要一个具有抗R和抗P互补位的多识别单T细胞抗原受体（TCR），二者协同发挥作用以发出限制性反应性信号。这种“双库”假说的结果不仅为我们提供了一个与目前普遍接受的TCR结构截然不同的概念，而且还解决了许多现存的矛盾。文中讨论了阳性和阴性选择、同种异体反应性、自身-非自身（S-NS）区分、库的性质和大小以及相关实验解释等问题。此外，还将三表位模型与先前提出的模型进行了比较，以说明为何需要一个与之竞争的模型。
