Merkenschlager M, Benoist C, Mathis D
Laboratory of Molecular Genetics of Eukaryotes, INSERM U184, Strasbourg, France.
J Immunol. 1994 Oct 1;153(7):3005-13.
The naive T cell repertoire is shaped by interactions between developing thymocytes and thymic stroma. Both positive and negative selection involve the clonotypic TCR and MHC molecules carrying self-peptides. Except for the MHC-dependent effects of superantigens on TCR V beta usage; there has been little evidence that the TCR structure of naive T cell varies with the selecting MHC products. To examine this point from another angle, in particular the TCR alpha-chain, we have analyzed alpha-chain usage in a system in which the vast majority of T cells express a transgene-encoded TCR beta-chain, compatible with efficient T cell development on a wide range of MHC haplotypes. Endogenous TCR alpha-chains are thus selected without interference from the forces known to act on TCR-beta, permitting us to observe MHC influences on alpha-chain selection. We have used V alpha-specific Abs to quantitate alpha-chain usage in MHC congenic, MHC recombinant, and MHC transgenic mice and provide evidence that the naive TCR alpha-chain repertoire is under MHC control. The data demonstrate a direct impact of known MHC class II products but also reflect more complex influences, apparently involving other gene products within the MHC. Sequence analysis of differentially selected TCR suggests that selection acts on the entire alpha-chain, including V alpha, J alpha, and the junctional region.
初始T细胞库是由发育中的胸腺细胞与胸腺基质之间的相互作用形成的。阳性和阴性选择都涉及携带自身肽段的克隆型TCR和MHC分子。除了超抗原对TCR Vβ使用的MHC依赖性影响外，几乎没有证据表明初始T细胞的TCR结构会随着所选择的MHC产物而变化。为了从另一个角度，特别是从TCRα链的角度来研究这一点，我们在一个系统中分析了α链的使用情况，在该系统中，绝大多数T细胞表达转基因编码的TCRβ链，这与在多种MHC单倍型上高效的T细胞发育是相容的。因此，内源性TCRα链的选择不受已知作用于TCR-β的力量的干扰，这使我们能够观察到MHC对α链选择的影响。我们使用Vα特异性抗体来定量分析MHC同基因、MHC重组和MHC转基因小鼠中α链的使用情况，并提供证据表明初始TCRα链库受MHC控制。数据表明已知的MHC II类产物有直接影响，但也反映了更复杂的影响，显然涉及MHC内的其他基因产物。对差异选择的TCR的序列分析表明，选择作用于整个α链，包括Vα、Jα和连接区。
