Human monoclonal antibody with T‐cell‐like specificity recognizes MHC class I self‐peptide presented by HLA‐DR1 on activated cells

: Alloreactive T cells recognize peptides presented in the binding groove of major histocompatibility complex molecules (MHCs), whereas B cells mainly recognize the MHCs independent of bound peptides. Here, we demonstrate that the human B-cell repertoire comprises B cells which can be stimulated during pregnancy to produce antibodies reacting with MHCs in a way similar to T cells. The human monoclonal antibody UL-5A1 recognizes DR1PRA/DRB1*0101) molecules on lymphoblastoid cell lines only if they co-express HLA-A2 or if they have been loaded with HLA-A2-derived peptides. The effect of the HLA-A2 peptide 105–117 on UL-5A1 reactivity was specific, time and dose-dependent Reactivity increased when naturally processed peptides were removed from DR1 molecules before the HLA-A2 peptide 105–117 was loaded. UL-5A1 reacted specifically with cells that had been activated. The results imply a role of activation of cells in peptide processing and/or loading.