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 β chain of human histocompatibility leukocyte antigen‐DQw5/w6 in antigen presentation to a hepatitis B surface antigen‐specific Tcell clone was studied. The results obtained demonstrate that the residue situated at position 57 of the β 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 Tcell 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 Tcell 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 Tcell responses and peptide blocking approaches in autoimmunity are discussed.