It was demonstrated previously that a
peptide derived from a conserved region of MHC class II,
HLA-DQA1, inhibits proliferation of allogeneic T cells in vitro. Administration of
HLA-DQA1 in conjunction with allogeneic cells at the time of priming or at the time of rechallenge prevented the development of the delayed type
hypersensitivity response in vivo. The immunomodulatory effects of
HLA-DQA1 were associated with the induction of apoptosis in B cells, macrophages, and dendritic cells via a
caspase-independent pathway. This study investigated the binding site and mechanism that mediates cell death induced by
HLA-DQA1. It was demonstrated that
HLA-DQA1 binds to MHC class II on the cell surface, causing MHC class II signaling, initiation of
protein kinase C signaling, and mitochondrial membrane depolarization with resultant apoptosis. The data indicate that
HLA-DQA1 binds to MHC class II outside the groove, in a manner similar to
superantigen. These results suggest that
HLA-DQA1 is a novel
immunotherapy that may provide an effective means of targeting professional antigen-presenting cells, in particular B cells.