Moudgil K D, Sekiguchi D, Kim S Y, Sercarz E E
Department of Microbiology and Molecular Genetics, University of California, Los Angeles 90095, USA.
J Immunol. 1997 Sep 15;159(6):2574-9.
T cell responses to different protein Ags have been shown to focus on a few ("immunodominant") determinants. We have addressed three major, interrelated questions regarding immunodominance. First, can each area within hen eggwhite lysozyme (HEL) serve as an immunodominant focus in different inbred mouse strains or are there structural constraints that limit the utilization of certain segments of the molecule? Second, in MHC-congenic mice with identical non-MHC genes, is response to HEL restricted to one or more members of a set of HEL determinants owing to processing constraints imposed by the background genes? Third, does a truncated TCR repertoire influence the immunodominance of certain determinants of HEL? Our results in 19 strains of mice, representing 11 different MHC haplotypes, demonstrate that the immunodominant determinants within HEL are distributed all over the molecule, suggesting that there is no inherent structural constraint imposed on certain regions to be always immunorecessive. However, in different mouse strains, the emergence of identical regions of HEL as immunodominant sites strictly correlates with the identity of their MHC haplotypes but not genetic background (non-MHC) genes. We attribute this relationship to "MHC-guided processing" of native Ag. Finally, our results demonstrate that a truncated TCR repertoire can result not only in the loss of response to certain immunodominant determinants, but can also result in a gain. These results should contribute significantly to further understanding of the mechanism of immunodominance.
已证明T细胞对不同蛋白质抗原的反应集中于少数几个（“免疫显性”）决定簇。我们针对免疫显性提出了三个主要的、相互关联的问题。第一，鸡卵清溶菌酶（HEL）内的每个区域在不同近交系小鼠品系中都能作为免疫显性焦点吗？还是存在结构限制，限制了分子某些片段的利用？第二，在具有相同非MHC基因的MHC同基因小鼠中，由于背景基因施加的加工限制，对HEL的反应是否限于一组HEL决定簇中的一个或多个成员？第三，截短的T细胞受体库会影响HEL某些决定簇的免疫显性吗？我们对代表11种不同MHC单倍型的19个小鼠品系的研究结果表明，HEL内的免疫显性决定簇分布于整个分子，这表明对某些区域不存在总是使其处于免疫隐性的内在结构限制。然而，在不同小鼠品系中，HEL相同区域作为免疫显性位点的出现与它们的MHC单倍型而非遗传背景（非MHC）基因的一致性严格相关。我们将这种关系归因于天然抗原的“MHC引导加工”。最后，我们的结果表明，截短的T细胞受体库不仅会导致对某些免疫显性决定簇的反应丧失，还可能导致反应增强。这些结果应会对进一步理解免疫显性机制有显著贡献。
