Immune response to peptides from the third hypervariable region of the beta chain of MHC class II molecules. Implications for the immune response to foreign antigens.

To understand the biologic significance of amino acid sequence sharing between proteins from pathogens and hypervariable regions of HLA DR molecules, we studied the immunological status of a peptide from the third hypervariable region of IEb, the mouse equivalent of HLA DRb. We found that allo MHC peptides are recognized and self MHC peptide is tolerated. This suggests that MHC class II molecules may modulate the T cell repertoire not only by selective binding of antigenic peptides (determinant selection) but also by deleting or inactivating T cells specific for self MHC peptides. In the human, such a mechanism may explain why some HLA DR4 subjects have a deficient control of EBV infection.