MHCクラスII分子を介したシグナル伝達と免疫制御

―免疫応答遺伝子再訪―

抄録

Signals transmitted by class II MHC molecules are important regarding cell function related to antigen presentation. Cross-linking HLA-DR molecules on B cells led to an increased production of IgM, with an enhanced expression of both membrane-and secretory-type IgM heavy chain mRNA. Increased IgM production was also observed in TCR-peptide-HLA-DR interaction, without the involvement of CD40-CD154 interaction. This event was inhibited specifically by piceatannol but not by PP 2, and ligation of HLA-DR on B cells enhanced Syk activity. Thus, HLA-DR molecules on B cells not only present antigenic peptides to T cells, but also upregulate IgM production, in association with Syk activation. We next found that peptide-pulsed monocytes preferentially produce proinflammatory monokines, by interacting with emetine-treated and DR-restricted T cells, whereas both DQ-restricted and DP-restricted T cells stimulated relatively higher levels of antiinflammatory monokine IL-10. Moreover, activation patterns of MAP kinases by anti-DR, anti-DQ and anti-DP Abs were distinct, which was further evidenced by the effect of MAP kinase inhibitors. HLA-DR, -DQ and -DP molecules may transmit distinct signals into monocytes through distinct MAP kinases and are functionally heterogeneous, which provide a clue to the need for generation of a multigene family of class II MHC.