ALTERED ANTIGEN PRESENTATION IN MICE LACKING H2-O

HLA-DM catalyzes the release of MHC class II-associated invariant chai n-derived peptides (CLIP) from class II molecules. Recent evidence has suggested that HLA-DO is a negative regulator of HLA-DM in B cells, b ut the physiological function of HLA-DO remains unclear. Analysis of a ntigen presentation by B cells from mice lacking H2-O (the mouse equiv alent of HLA-DO), together with biochemical analysis using purified HL A-DO and HLA-DM molecules, suggests that HLA-DO/H2-O influences the pe ptide loading of class II molecules by limiting the pH range in which HLA-DM is active. This effect may serve to decrease the presentation o f antigens internalized by fluid-phase endocytosis, thus concentrating the B cell-mediated antigen presentation to antigens internalized by membrane immunoglobulin.