Kaye J, Hedrick S M
Department of Biology, University of California, San Diego, La Jolla 92093.
Nature. 1988 Dec 8;336(6199):580-3. doi: 10.1038/336580a0.
The majority of peripheral T lymphocytes bear cell-surface antigen receptors comprised of a disulphide-linked alpha beta dimer. In an immune response, this receptor endows T cells with specificities for foreign antigenic protein fragments bound to cell surface glycoproteins encoded in the major histocompatibility complex (MHC). At a high frequency (greater than 1%), the same population of T lymphocytes responds to allogeneic MHC glycoproteins, or to differences at other genetic loci termed Mls, in conjunction with MHC. The alpha beta-antigen receptor has been implicated in alloreactivity and Mls reactivity. In fact, many monoclonal T-cell lines recognize a foreign protein fragment bound to self-MHC molecules and, in addition, recognize allogeneic MHC glycoproteins, an Mls-encoded determinant, or both. For at least one T-cell clone, a monoclonal antibody directed against the alpha beta antigen receptor has been shown to block activation induced by either antigen-bound self-MHC or by allogeneic MHC. However, it remains to be demonstrated directly that a single alpha beta receptor can mediate antigen specificity, alloreactivity and Mls reactivity, a prerequisite to understanding the structural basis of these high-frequency cross-reactivities. To address this issue we have performed transfers of receptor chain genes from a multiple-reactive T-cell clone into an unrelated host T lymphocyte. We now demonstrate definitively that the genes encoding a single alpha beta-receptor chain pair can transfer the recognition of self-MHC molecules complexed with fragments of antigen, allogeneic MHC molecules, and an Mls-encoded determinant (presumably in conjunction with MHC). In this case the transfer of antigen specificity and alloreactivity requires a specific alpha beta-receptor chain combination, whereas Mls reactivity can be transferred with the beta-chain gene alone into a recipient expressing a randomly selected alpha-chain.
大多数外周T淋巴细胞带有由二硫键连接的αβ二聚体组成的细胞表面抗原受体。在免疫反应中，该受体赋予T细胞对与主要组织相容性复合体（MHC）编码的细胞表面糖蛋白结合的外来抗原性蛋白片段的特异性。同一群T淋巴细胞以高频率（大于1%）对同种异体MHC糖蛋白，或对与MHC相关的其他称为Mls的基因座差异作出反应。αβ抗原受体与同种异体反应性和Mls反应性有关。事实上，许多单克隆T细胞系识别与自身MHC分子结合的外来蛋白片段，此外，还识别同种异体MHC糖蛋白、Mls编码的决定簇或两者。对于至少一个T细胞克隆，已证明一种针对αβ抗原受体的单克隆抗体可阻断由抗原结合的自身MHC或同种异体MHC诱导的激活。然而，仍有待直接证明单个αβ受体可介导抗原特异性、同种异体反应性和Mls反应性，这是理解这些高频交叉反应结构基础的先决条件。为了解决这个问题，我们将受体链基因从一个多反应性T细胞克隆转移到一个不相关的宿主T淋巴细胞中。我们现在明确证明，编码单个αβ受体链对的基因可以转移对与抗原片段复合的自身MHC分子、同种异体MHC分子和Mls编码的决定簇（可能与MHC相关）的识别。在这种情况下，抗原特异性和同种异体反应性的转移需要特定的αβ受体链组合，而Mls反应性可以仅通过β链基因转移到表达随机选择的α链的受体中。
