Pawlowski T J, Singleton M D, Loh D Y, Berg R, Staerz U D
Department of Medicine, National Jewish Center of Immunology and Respiratory Medicine, Denver, CO 80206, USA.
Eur J Immunol. 1996 Apr;26(4):851-7. doi: 10.1002/eji.1830260419.
In the periphery alpha beta T lymphocytes recognize antigens in conjunction with major histocompatibility complex (MHC) molecules. In the thymus immature T cells are positively selected on MHC molecules in the apparent absence of cognate peptides. Thus, at different developmental stages a T cell responds to different epitopes, yet uses the identical alpha beta T cell antigen receptor (TcR). To explain this paradox it has been hypothesized that during positive selection immature T cells see peptides/ligands unique to the thymus, are selected by specific antagonists related to their cognate peptides, or are driven by lowered affinity thresholds of their TcR. Though different in detail, these theories rely on defined peptides uniquely matched to select certain TcR. However, we find that in a TcR-transgenic (TcR(trans +)) mouse severely limiting the diversity of peptides does not impair positive selection. We show that many unrelated peptides, including some naturally occurring on the cell surface, induce maturation of CD4-CD8+TcR(high) thymocytes. The same peptides when presented in conjunction with the selecting MHC molecule, are not recognized by peripheral T cells expressing the same TcR(trans). Therefore, these findings point to a promiscuous rather than discriminate recognition mode used by immature T cells.
在外周，αβ T淋巴细胞与主要组织相容性复合体（MHC）分子共同识别抗原。在胸腺中，未成熟T细胞在明显缺乏同源肽的情况下在MHC分子上进行阳性选择。因此，在不同的发育阶段，T细胞对不同的表位作出反应，但使用相同的αβ T细胞抗原受体（TcR）。为了解释这一矛盾现象，有人提出在阳性选择过程中，未成熟T细胞识别胸腺特有的肽/配体，被与其同源肽相关的特异性拮抗剂所选择，或者被其TcR降低的亲和力阈值所驱动。尽管细节不同，但这些理论都依赖于特定的肽与特定的TcR进行独特匹配。然而，我们发现在TcR转基因（TcR（trans +））小鼠中，严重限制肽的多样性并不损害阳性选择。我们发现许多不相关的肽，包括一些细胞表面天然存在的肽，可诱导CD4-CD8+TcR（高）胸腺细胞成熟。当这些相同的肽与选择的MHC分子一起呈递时，表达相同TcR（trans）的外周T细胞并不能识别它们。因此，这些发现表明未成熟T细胞使用的是一种混杂而非特异性的识别模式。
