Tam R C, Fedoseyeva E V, Moskalenko M, Garovoy M R, Benichou G
Department of Surgery, University of California at San Francisco 94143, USA.
J Immunol. 1996 May 15;156(10):3765-71.
Although the current dogma of T cell recognition stresses its exquisite specificity, T cell clones selected for a given peptide can recognize other sequentially or structurally related peptides. Here, we have examined the immunogenicity and tolerogenicity of various self-peptides derived from region 61-80 of different MHC class I proteins co-expressed in the same mouse. Following immunization of B10.A mice (K(k), A(k), E(k), L(d), D(d)) with self-L(d) 61-80 peptide, vigorous MHC class II-restricted T cell proliferation was elicited after restimulation with either the immunogen or with self-K(k) 61-80 but not with self-D(d) 61-80. Furthermore, adult B10.A mice, tolerized with L(d) 61-80 prior to immunization with L(d) 61-80 did not respond to challenge with L(d) 61-80 and the cross-reactive K(k) 61-80. However, following K(k) 61-80 immunization, L(d) 61-80-tolerized mice responded to K(k) 61-80 but not to L(d) 61-80. Thus, tolerance induction to L(d) 61-80 resulted in the elimination/inactivation of L(d) 61-80-reactive T cells including the subpopulation that cross-reacted with K(k) 61-80. However, T cells that recognized K(k) 61-80 exclusively were preserved. Moreover, we showed that immunization with K(k) 61-80 resulted in tolerance breakdown to the cross-reactive, dominant self-peptide D(b) 61-80 in B10.A(4R) mice (K(k), A(k), L(d),D(b)). Together, these results show that the autoimmune T cell repertoire is influenced by the concomitant recognition of different cross-reactive self-peptides within the same individual.
尽管目前关于T细胞识别的教条强调其高度特异性，但针对给定肽段筛选出的T细胞克隆能够识别其他序列或结构相关的肽段。在此，我们研究了在同一小鼠中共表达的不同MHC I类蛋白61 - 80区域衍生的各种自身肽段的免疫原性和耐受性。用自身L(d) 61 - 80肽免疫B10.A小鼠（K(k)、A(k)、E(k)、L(d)、D(d)）后，用免疫原或自身K(k) 61 - 80再次刺激可引发强烈的MHC II类限制性T细胞增殖，但用自身D(d) 61 - 80刺激则不会。此外，成年B10.A小鼠在先用L(d) 61 - 80进行耐受性诱导后，再用L(d) 61 - 80进行免疫，对L(d) 61 - 80和交叉反应性的K(k) 61 - 80的攻击均无反应。然而，在用K(k) 61 - 80免疫后，L(d) 61 - 80耐受性小鼠对K(k) 61 - 80有反应，但对L(d) 61 - 80无反应。因此，对L(d) 61 - 80的耐受性诱导导致了L(d) 61 - 80反应性T细胞的消除/失活，包括与K(k) 61 - 80交叉反应的亚群。然而，仅识别K(k) 61 - 80的T细胞得以保留。此外，我们还表明，用K(k) 61 - 80免疫会导致B10.A(4R)小鼠（K(k)、A(k)、L(d)、D(b)）对交叉反应性的、占主导地位的自身肽段D(b) 61 - 80的耐受性破坏。总之，这些结果表明，自身免疫性T细胞库受到同一个体内不同交叉反应性自身肽段的伴随识别的影响。
