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.
Serra
H M
HM
Cytel, San Diego, CA 92121.
Crimi
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C
Sette
A
A
Celis
E
E
D000595:Amino Acid Sequence; D000938:Antigen-Presenting Cells / Q000276:immunology; D001667:Binding, Competitive; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002999:Clone Cells / Q000276:immunology; D006683:HLA-DQ Antigens / Q000235:genetics / Q000378:metabolism; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors
D006683:HLA-DQ Antigens; D006514:Hepatitis B Surface Antigens; D010446:Peptide Fragments; D011498:Protein Precursors; D011948:Receptors, Antigen, T-Cell; C050806:presurface protein 1, hepatitis B surface antigen