CD26 up-regulates expression of CD86 on antigen-presenting cells by means of caveolin-1
CD26 up-regulates expression of CD86 on antigen-presenting cells by means of caveolin-1
复制标题
DOI：
10.1073/pnas.0405266101
复制
发表时间：
2004-09-28
影响因子：
11.1
通讯作者：
Morimoto, C
中科院分区：
文献类型：
--
作者：
Ohnuma, K;Yamochi, T;Morimoto, C
CD26是一种T细胞共刺激分子，胞外区具有二肽基肽酶IV活性。我们曾报道重组可溶性CD26能增强破伤风类毒素(TT)诱导的T细胞增殖。然而，这种增强的机制尚未阐明。我们现在证明CD26与抗原提呈细胞上的小凹-1结合，并且CD26的201-211残基以及630位的丝氨酸催化位点有助于与小窝-1支架结构域的结合。此外，CD26-小窝蛋白-1与TT负载的单核细胞相互作用后，小窝蛋白-1被磷酸化，从而激活了核因子-kappaB，随后上调了CD86。最后，减少单核细胞上小凹蛋白-1的表达可抑制CD26介导的CD86上调，并取消CD26对TT诱导的T细胞增殖的影响。综上所述，这些结果有力地表明，CD26-小窝蛋白-1的相互作用在TT负载的单核细胞上CD86的上调以及随后与T细胞上的CD28结合导致抗基因特异性T细胞激活中起作用。
CD26 is a T cell costimulatory molecule with dipeptidyl peptidase IV activity in its extracellular region. We previously reported that recombinant soluble CD26 enhanced T cell proliferation induced by the recall antigen tetanus toxoid (TT). However, the mechanism involved in this enhancement is not yet elucidated. We now demonstrate that CD26 binds Caveolin-1 on antigen-presenting cells, and that residues 201-211 of CD26 along with the serine catalytic site at residue 630 contribute to binding to caveolin-1 scaffolding domain. In addition, after CD26-caveolin-1 interaction on TT-loaded monocytes, caveolin-1 is phosphorylated, which links to activate NF-kappaB, followed by up-regulation of CD86. Finally, reduced caveolin-1 expression on monocytes inhibits CD26-mediated CD86 up-regulation and abrogates CD26 effect on TT-induced T cell proliferation. Taken together, these results strongly suggest that CD26-caveolin-1 interaction plays a role in the up-regulation of CD86 on TT-loaded monocytes and subsequent engagement with CD28 on T cells, leading to anti gen-specific T cell activation.