Hardardottir F, Baron J L, Janeway C A
Section of Immunobiology, Yale University School of Medicine, New Haven, CT.
Proc Natl Acad Sci U S A. 1995 Jan 17;92(2):354-8. doi: 10.1073/pnas.92.2.354.
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.
尽管克隆选择理论指出淋巴细胞应该仅携带单一特异性的受体，但有大量证据表明至少一些T细胞携带两种受体。在此，我们利用转基因小鼠来编码自身反应性T细胞受体（TCR），以研究携带两种功能性TCR的T细胞的特异性。我们发现，在不表达转基因编码的TCR所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，也表达对其产生的品系的MHC分子具有特异性的第二种TCR。因此，这些T细胞有两种TCR，每种TCR对与不同MHC分子结合的不同抗原具有特异性。相比之下，当在携带受体所特异性识别的MHC的小鼠中培育时，发育出的T细胞几乎只表达转基因编码的TCR。这样的小鼠对自身免疫性疾病高度易感。我们的数据表明，在大多数携带两种TCR的T细胞上，只有一种对与自身MHC分子结合的肽具有特异性，因此，两种TCR的表达通常不会赋予对两种不相关抗原的反应性。
