Fine restriction analysis and inhibition of antigen recognition in HLA-DQ-restricted T cells by major histocompatibility complex blockers and T cell receptor antagonists.

The role of polymorphic residues of the beta chain of human histocompatibility leukocyte antigen-DQw5/w6 in antigen presentation to a hepatitis B surface antigen-specific T cell clone was studied. The results obtained demonstrate that the residue situated at position 57 of the beta chain (a valine) is critical for presentation of antigen by antigen-presenting cells to the DQ-restricted T cell clone. Experiments were also done to study the feasibility of peptide blocking of antigen recognition by DQ-restricted T cells. The results indicate that peptides known to associate with DQ molecules are capable of blocking the presentation of antigen to the DQ-restricted T cell clone, presumably by competing with antigen for binding to major histocompatibility complex (MHC) molecules. Moreover, truncations of the stimulatory antigenic peptide resulted in the production of T cell receptor antagonists, which inhibited the response of the T cells to antigen at 10-100-fold lower concentrations than conventional MHC blockers. The role of DQ-restricted T cell responses and peptide blocking approaches in autoimmunity are discussed.