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T 淋巴细胞与 B 淋巴细胞之间的直接受体-受体相互作用:对克隆的辅助性 T 细胞受体抗体应答中的独特型限制

Direct receptor:receptor interactions between T and B lymphocytes: idiotypic restriction in the antibody response to a cloned helper T cell receptor.

作者信息

Janeway C A, Broughton B, Smith L A, Marion T N, Bottomly K

机构信息

Department of Pathology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510.

出版信息

J Mol Cell Immunol. 1987;3(2):83-94.

PMID:2978239
Abstract

The concept of an immunological network includes the possibility of interactions between receptors on T and B lymphocytes, and such interactions, should they occur, might be expected to influence the repertoire of receptors in each set of cells. Indeed, B cell idiotype specific helper T cells, both MHC-restricted and MHC-unrestricted, have been reported and have been shown to influence the expression of the B cell repertoire. Likewise, it has been reported that B cells may influence the specificity of both regulatory and MHC-restricted T cells. However, interactions between receptors on cloned, MHC-restricted helper T cells and B cells have been difficult to document. Recently, we have taken advantage of an unusual cloned helper T cell line to demonstrate that anti-T cell receptor antibody is produced by direct receptor:receptor interactions between T and B lymphocytes, and that these interactions are not MHC restricted. However, these earlier studies did not address the question of whether such interactions led to activation of B cells expressing multiple distinct antibodies, or whether direct T cell receptor:B cell receptor interactions would lead to an idiotypically restricted B cell response. To address this question, we have now examined both monoclonal and polyclonal responses to the receptor of a conventional, MHC-restricted cloned T cell line, and have shown that these responses are of limited idiotype heterogeneity. Indeed, about 60% of antibodies produced to the receptor of this cloned line share idiotypic determinants, and appear to recognize a single epitope on the receptor. Idiotypically unrelated anti-receptor antibodies, although still specific for the cloned line, recognize what appears to be a distinct epitope on the receptor. These data suggest several conclusions. First, they demonstrate further that direct receptor:receptor interactions between helper T cells and B cells can occur, and can be mutually stimulatory for the two cell types. Second, as shown previously, such interactions are not MHC restricted. Third, such interactions can lead to an idiotypically restricted B cell response. Finally, it is interesting to compared these results with those of other investigators studying idiotype-specific helper T cells. As the cloned line used in this study is a conventional, MHC-restricted, antigen specific helper T cell bearing an alpha:beta heterodimeric receptor complex, and as its interaction with B cells is MHC unrestricted and leads to idiotypically restricted antibody responses, one might propose that such cells are candidates for a clone of an idiotype-specific helper.(ABSTRACT TRUNCATED AT 400 WORDS)

摘要

免疫网络的概念包括T淋巴细胞和B淋巴细胞上的受体之间相互作用的可能性,而且如果发生这种相互作用,可能会影响每组细胞中受体的种类。实际上,已经报道了受MHC限制和不受MHC限制的B细胞独特型特异性辅助性T细胞,并且已表明它们会影响B细胞受体库的表达。同样,也有报道称B细胞可能会影响调节性T细胞和受MHC限制的T细胞的特异性。然而,克隆的、受MHC限制的辅助性T细胞与B细胞上的受体之间的相互作用一直难以证实。最近,我们利用一种特殊的克隆辅助性T细胞系证明,抗T细胞受体抗体是由T淋巴细胞和B淋巴细胞之间直接的受体:受体相互作用产生的,并且这些相互作用不受MHC限制。然而,这些早期研究没有解决这样的相互作用是否会导致表达多种不同抗体的B细胞活化的问题,或者直接的T细胞受体:B细胞受体相互作用是否会导致独特型受限的B细胞反应的问题。为了解决这个问题,我们现在研究了对一个传统的、受MHC限制的克隆T细胞系的受体的单克隆和多克隆反应,并且已经表明这些反应的独特型异质性有限。实际上,针对这个克隆系的受体产生的抗体中约60%共享独特型决定簇,并且似乎识别该受体上的单个表位。独特型不相关的抗受体抗体虽然仍然对该克隆系具有特异性,但识别的似乎是该受体上一个不同的表位。这些数据表明了几个结论。首先,它们进一步证明了辅助性T细胞和B细胞之间可以发生直接的受体:受体相互作用,并且对这两种细胞类型可以是相互刺激的。其次,如先前所示,这种相互作用不受MHC限制。第三,这种相互作用可以导致独特型受限的B细胞反应。最后,将这些结果与其他研究独特型特异性辅助性T细胞的研究者的结果进行比较是很有意思的。由于本研究中使用的克隆系是一个传统的、受MHC限制的、携带α:β异二聚体受体复合物的抗原特异性辅助性T细胞,并且由于它与B细胞的相互作用不受MHC限制并导致独特型受限的抗体反应,有人可能会提出这样的细胞是独特型特异性辅助性细胞克隆的候选者。(摘要截短至400字)

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