T cells with two functional antigen-specific receptors.
T cells with two functional antigen-specific receptors.
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T 细胞具有两种功能性抗原特异性受体。
DOI：
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发表时间：
1995
影响因子：
11.1
通讯作者：
Charles A. Janeway
中科院分区：
文献类型：
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作者：
F. Hardardottir;Jody L. Baron;Charles A. Janeway
虽然克隆选择理论认为淋巴细胞应该只携带一种受体的特异性，但有很多证据表明，至少有些T细胞携带两种受体。在这里，我们使用了编码自身反应性T细胞受体(TCR)基因的小鼠来检测携带两个功能TCR的T细胞的特异性。我们发现，在不表达转基因编码的TCR识别为自身的主要组织相容性复合体(MHC)分子的小鼠中发育的T细胞既表达这种TCR，又表达第二个TCR，后者是出现这种TCR的菌株的MHC分子所特有的。因此，这些T细胞有两个TCR，每个TCR针对不同的抗原与不同的MHC分子结合。相反，当在携带受体特异性MHC的小鼠中长大时，T细胞几乎完全表达转基因编码的TCR。这类小鼠极易感染自身免疫性疾病。我们的数据表明，在大多数携带两个TCR的T细胞上，只有一个是与自身MHC分子结合的多肽特异的，因此，两个TCR的表达通常不会对两个无关的抗原产生反应性。
Although the clonal selection theory states that lymphocytes should bear only a single specificity of receptor, there is much evidence that some T cells, at least, bear two receptors. Here, we have used mice transgenic for genes encoding an autoreactive T-cell receptor (TCR) to examine the specificity of T cells bearing two functional TCRs. We find that T cells developing in mice that do not express the major histocompatibility complex (MHC) molecule recognized as self by the transgene-encoded TCR express both this TCR and a second TCR that is specific for the MHC molecules of the strain in which it arose. Thus, these T cells have two TCRs, each specific for a distinct antigen bound to a distinct MHC molecule. In contrast, when raised in mice bearing the MHC for which the receptor is specific, T cells develop that express the transgene-encoded TCR almost exclusively. Such mice are highly susceptible to autoimmune disease. Our data suggest that on most T cells bearing two TCRs, only one is specific for peptides bound to self-MHC molecules and, thus, that expression of two TCRs does not usually confer reactivity to two unrelated antigens.