H2-O influence on antigen presentation in H2-E-expressing mice

MHC class II molecules sample peptides generated in the endosomal/lysosomal system for cell surface presentation to CD4(+) T cells. Peptide loading requires the endosomal/lysosomal resident HLA-DM (DM; H2-DM, mouse), but in B cells, DM is tightly associated with HLA-DO (DO; H2-O, mouse). We have previously shown that H2-O differentially modulates the processing and presentation of different antigenic epitopes on H2-A(b) molecules. Using H2-Ea(d)-transgenic mice, we here show that presentation of different epitopes by H2-E-d/b molecules is similarly influenced by H2-O after membrane immunoglobulin-mediated uptake of antigen. In addition, B cells from H2-Ea(d)-transgenic mice (which co-express H2-A(b) and H2-E-d/b molecules) show an altered pattern of presentation of H2-A(b)-restricted epitopes. In H2-Ea(d)-transgenic, H2-O-deficient mice, further changes in the peptide repertoire were observed. Thus, H2-E-d/b expression influences the epitopes presented by H2-A(b), and this effect is further altered by expression of H2-O.