Mackewicz C E, Leung C Y, Benjamini E
Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis 95616.
Cell Immunol. 1989 Nov;124(1):119-31. doi: 10.1016/0008-8749(89)90116-0.
We have previously shown that sc immunization of C57BL/10 (H-2b) mice with the tobacco mosaic virus protein (TMVP) or with its tryptic peptide number 8, representing residues 93-112 of TMVP, induces T cells which proliferate in vitro in response to TMVP and to peptide 8. In contrast, immunization of B10.BR (H-2k) mice either with TMVP or with peptide 8 induces T cells which respond in vitro to the homologous but not the heterologous Ag. In the present article , we report that in the B10.BR (H-2k) strain, ip prepriming with (TMVP) 7 days prior to sc immunization with peptide 8 causes a drastic reduction in the in vitro proliferative response of peptide 8-specific T cells while no such effect is seen in the congenic C57BL/10 (H-2b) strain. This suppression of T cell responsiveness can be transferred with TMVP-primed spleen cells. Moreover, deleting T cells from the transferred spleen cells abrogates the suppressive effect. In both H-2 haplotypes, ip prepriming with peptide 8 causes suppression of the proliferative T cell response induced by subsequent immunization with peptide 8. This prepriming has no effect on the response to TMVP immunization of B10.BR mice but does effect the response of C57BL/10 mice. Using various synthetic peptides to analyze the specificity of the suppression, we have determined that (1) T cells involved in the suppression of the proliferative T cell response to a single peptide determinant do not suppress the proliferative T cell response to other determinants on the protein antigen and (2) these T cells with suppressor function, and proliferating T cells which are ultimately regulated, can exhibit specificity for the same epitope. These studies suggest that there may exist fundamental differences as to how T cells which participate in suppression an proliferating T cells (which include mainly T helper cells) recognize protein antigens.
我们先前已表明，用烟草花叶病毒蛋白（TMVP）或其胰蛋白酶肽段8（代表TMVP的93 - 112位残基）对C57BL/10（H-2b）小鼠进行皮下免疫，可诱导T细胞在体外对TMVP和肽段8产生增殖反应。相比之下，用TMVP或肽段8对B10.BR（H-2k）小鼠进行免疫，可诱导T细胞在体外对同源抗原而非异源抗原产生反应。在本文中，我们报道，在B10.BR（H-2k）品系中，在皮下用肽段8免疫前7天腹腔注射预激发（TMVP）会导致肽段8特异性T细胞的体外增殖反应急剧降低，而在同基因的C57BL/10（H-2b）品系中未观察到这种效应。T细胞反应性的这种抑制可通过TMVP预激发的脾细胞进行转移。此外，从转移的脾细胞中去除T细胞可消除抑制作用。在两种H-2单倍型中，腹腔注射肽段8进行预激发会抑制随后用肽段8免疫诱导的T细胞增殖反应。这种预激发对B10.BR小鼠对TMVP免疫的反应没有影响，但对C57BL/10小鼠的反应有影响。使用各种合成肽分析抑制的特异性，我们确定：（1）参与抑制对单个肽决定簇的T细胞增殖反应的T细胞不会抑制对蛋白质抗原上其他决定簇的T细胞增殖反应；（2）这些具有抑制功能的T细胞以及最终被调节的增殖T细胞可对相同表位表现出特异性。这些研究表明，参与抑制增殖T细胞（主要包括T辅助细胞）的T细胞识别蛋白质抗原的方式可能存在根本差异。
