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Encounter with antigen-specific primed CD4 T cells promotes MHC class II degradation in dendritic cells

Furuta, Kazuyuki, Ishido, Satoshi, Roche, Paul A.
Proceedings of the National Academy of Sciences of the United States of America 2012 v.109 no.47 pp. 19380-19385
CD4-positive T-lymphocytes, antibodies, crosslinking, dendritic cells, endocytosis, immune response, lipids, lysosomes, major histocompatibility complex
Major histocompatibility complex class II molecules (MHC-II) on antigen presenting cells (APCs) engage the TCR on antigen-specific CD4 T cells, thereby providing the specificity required for T cell priming and the induction of an effective immune response. In this study, we have asked whether antigen-loaded dendritic cells (DCs) that have been in contact with antigen-specific CD4 T cells retain the ability to stimulate additional naïve T cells. We show that encounter with antigen-specific primed CD4 T cells induces the degradation of surface MHC-II in antigen-loaded DCs and inhibits the ability of these DCs to stimulate additional naïve CD4 T cells. Cross-linking with MHC-II mAb as a surrogate for T-cell engagement also inhibits APC function and induces MHC-II degradation by promoting the clustering of MHC-II present in lipid raft membrane microdomains, a process that leads to MHC-II endocytosis and degradation in lysosomes. Encounter of DCs with antigen-specific primed T cells or engagement of MHC-II with antibodies promotes the degradation of both immunologically relevant and irrelevant MHC-II molecules. These data demonstrate that engagement of MHC-II on DCs after encounter with antigen-specific primed CD4 T cells promotes the down-regulation of cell surface MHC-II in DCs, thereby attenuating additional activation of naïve CD4 T cells by these APCs.