Ohnuma Kei, Yamochi Tadanori, Uchiyama Masahiko, Nishibashi Kunika, Yoshikawa Noritada, Shimizu Noriaki, Iwata Satoshi, Tanaka Hirotoshi, Dang Nam H, Morimoto Chikao
Department of Clinical Immunology, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, 4-6-1, Shirokanedai, Minato-Ku, Tokyo 108-8639, Japan.
Proc Natl Acad Sci U S A. 2004 Sep 28;101(39):14186-91. doi: 10.1073/pnas.0405266101. Epub 2004 Sep 7.
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 antigen-specific T cell activation.
CD26是一种T细胞共刺激分子,其细胞外区域具有二肽基肽酶IV活性。我们之前报道过,重组可溶性CD26可增强回忆抗原破伤风类毒素(TT)诱导的T细胞增殖。然而,这种增强作用所涉及的机制尚未阐明。我们现在证明,CD26与抗原呈递细胞上的小窝蛋白-1结合,并且CD26的201-211位氨基酸残基以及630位氨基酸残基处的丝氨酸催化位点有助于与小窝蛋白-1支架结构域结合。此外,在负载TT的单核细胞上发生CD26-小窝蛋白-1相互作用后,小窝蛋白-1被磷酸化,这与激活核因子κB相关联,随后CD86上调。最后,单核细胞上小窝蛋白-1表达的降低会抑制CD26介导的CD86上调,并消除CD26对TT诱导的T细胞增殖的作用。综上所述,这些结果强烈表明,CD26-小窝蛋白-1相互作用在负载TT的单核细胞上CD86的上调以及随后与T细胞上CD28的结合中发挥作用,从而导致抗原特异性T细胞活化。