Heber-Katz E, Hansburg D, Schwartz R H
Laboratory of Immunology, National Institutes of Allergy and Infectious Diseases, Bethesda, MD 20205.
J Mol Cell Immunol. 1983;1(1):3-18.
It is now clear that MHC-encoded molecules influence the immune response by their effects on T cell specificity. However, the mechanism(s) by which this occurs in an antigen-specific manner is not clear. Two broad categories of models have been proposed. One postulates that Ia molecules influence the T cell repertoire during ontogeny and that the clones of T cells capable of recognizing the antigen in association with the nonresponder Ia molecule are deleted or are never assembled. The other postulates that Ia molecules influence the immune response during T cell activation and that the clones of T cells capable of recognizing the antigen in association with the nonresponder Ia molecule are not stimulated because this Ia molecule does not bind or interact well with the antigen. Recent experiments by several laboratories have identified allogeneic T cell clones and populations capable of responding to an antigen in association with nonresponder Ia molecules. This result suggested that nonresponder Ia molecules are capable of interacting with antigen in a functional manner. Therefore it was inferred that Ir gene defects must lie in the T cell repertoire. However, we have recently discovered several mouse T cell clones whose characteristics suggest that this conclusion might not describe the complete picture. These clones have the unusual property of recognizing moth cytochrome c in association with either B10.A or B10.A(5R) Ia molecules, but they recognize pigeon cytochrome c only in associated with B10.A Ia molecules. Thus, the Ia-molecule-antigen interaction appears to be able to affect the fine specificity of the T cell activation process. Interestingly, the failure to respond to pigeon cytochrome c in association with B10.A(5R) Ia molecules correlates with the Ir gene control of the response to this antigen since the B10.A(5R) strain is a nonresponder to pigeon cytochrome c whereas the B10.A strain is a responder. The question we wished to address in this paper was whether the clones we had identified were representative of the T cell repertoires of both strains. If so, this would allow us to conclude that Ia molecule-antigen interactions during T cell activation could account for Ir gene control in certain situations. To answer the experimental question, we first examined several more T cell clones from [B10.A x B10.A(5R)]F1 and B10.A(5R) mice to solidify our previous findings. Then we turned to populations of T cells to determine if these findings could be generalized.(ABSTRACT TRUNCATED AT 400 WORDS)
现在已经清楚，主要组织相容性复合体（MHC）编码的分子通过对T细胞特异性的影响来影响免疫反应。然而，这一过程以抗原特异性方式发生的机制尚不清楚。已经提出了两大类模型。一类假设Ia分子在个体发育过程中影响T细胞库，并且能够识别与无反应性Ia分子相关抗原的T细胞克隆被删除或从未组装。另一类假设Ia分子在T细胞激活过程中影响免疫反应，并且能够识别与无反应性Ia分子相关抗原的T细胞克隆未被刺激，因为这种Ia分子不能与抗原良好结合或相互作用。几个实验室最近的实验已经鉴定出能够对与无反应性Ia分子相关的抗原作出反应的同种异体T细胞克隆和群体。这一结果表明无反应性Ia分子能够以功能性方式与抗原相互作用。因此推断免疫反应基因（Ir基因）缺陷必定存在于T细胞库中。然而，我们最近发现了几个小鼠T细胞克隆，其特征表明这一结论可能并不全面。这些克隆具有不同寻常的特性，即能够识别与B10.A或B10.A(5R) Ia分子相关的蛾细胞色素c，但它们仅能识别与B10.A Ia分子相关的鸽细胞色素c。因此，Ia分子 - 抗原相互作用似乎能够影响T细胞激活过程的精细特异性。有趣的是，不能对与B10.A(5R) Ia分子相关的鸽细胞色素c作出反应与对该抗原反应的Ir基因控制相关，因为B10.A(5R)品系对鸽细胞色素c无反应而B10.A品系有反应。我们在本文中想要解决的问题是，我们鉴定出的克隆是否代表这两个品系的T细胞库。如果是这样，这将使我们能够得出结论，T细胞激活过程中的Ia分子 - 抗原相互作用在某些情况下可以解释Ir基因控制。为了回答这个实验问题，我们首先检查了来自[B10.A×B10.A(5R)]F1和B10.A(5R)小鼠的更多T细胞克隆，以巩固我们之前的发现。然后我们转向T细胞群体，以确定这些发现是否可以推广。（摘要截选至400字）
