DM enhances peptide binding to class II MHC by release of invariant chain-derived peptide

MA Sherman, DA Weber, PE Jensen - Immunity, 1995 - cell.com
MA Sherman, DA Weber, PE Jensen
Immunity, 1995cell.com
Major histocompatibllity complex (MHC) class II molecules bind antigenic peptides rapidly
after biosynthesis in antigen-presenting cells (APCs). By contrast, the rate of peptide binding
to purified class II molecules is remarkably slow. We find that purified HLA-DR molecules
bind peptides rapidly in the presence but not the absence of HLA-DM, a recently identified
heterodlmer required for efficient antigen processing. The same effect is seen with
immunoprecipitated DM, suggesting that DM interacts directly with DR. Class II-associated …
Summary
Major histocompatibllity complex (MHC) class II molecules bind antigenic peptides rapidly after biosynthesis in antigen-presenting cells (APCs). By contrast, the rate of peptide binding to purified class II molecules is remarkably slow. We find that purified HLA-DR molecules bind peptides rapidly in the presence but not the absence of HLA-DM, a recently identified heterodlmer required for efficient antigen processing. The same effect is seen with immunoprecipitated DM, suggesting that DM interacts directly with DR. Class II-associated Invariant chain peptides (CLIP) are selectively and rapidly released from DR during incubation with DM at pH 5. We conclude that DM is a cofactor that enhances peptide binding to DR molecules through a mechanism involving peptide exchange.
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