Alloantigenic sites on class I major histocompatibility complex antigens: 61-69 region in the first domain of the H-2Kb molecule induces specific antibody and T cell responses.
The most polymorphic residues in the first domain of class I major histocompatibility complex (MHC) molecules are in the 61-69 region. We have chosen the H-2Kb molecule for determining the role of this region in the induction of alloimmune responses. A synthetic peptide, Glu-Arg-Glu-Thr-Gln-Lys-Ala-Lys-Gly corresponding to this region was synthesized. T cells enriched from the lymph nodes of allostrain mice that were previously primed with H-2Kb containing cells or with the synthetic peptide in complete Freund's adjuvant undergo extensive in vitro proliferation in response to the synthetic (61-69)H-2Kb peptide. The response was dependent on the presentation of the (61-69)H-2Kb peptide by the syngeneic antigen-presenting cells and was blocked by anti-class II MHC monoclonal antibodies. This peptide fragment of class I MHC molecule activates only helper/inducer type T cells that are involved in the primary responses but not the effector cytotoxic T cells. When coupled to a carrier protein, (61-69)H-2Kb peptide induced antibodies in allostrain mice that bind to intact H-2Kb molecule. No antibodies or T cell responses could be induced in syngeneic H-2b mice. The antigenic site on the H-2Kb molecule recognized by two H-2Kb-specific monoclonal antibodies B8 X 3 X 24 and Y-25 was also mapped in the 61-69 region by direct binding to the synthetic peptide. Therefore the 61-69 region on the H-2Kb molecule represents the first defined sequence on a class I molecule that is directly involved in the induction of alloimmune responses.
D000818:Animals; D000911:Antibodies, Monoclonal; D000939:Epitopes; D006183:H-2 Antigens / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007156:Immunologic Memory; D007518:Isoantibodies / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D010446:Peptide Fragments / Q000276:immunology; D011487:Protein Conformation; D013601:T-Lymphocytes / Q000276:immunology*; D014301:Trinitrobenzenes / Q000276:immunology
D000911:Antibodies, Monoclonal; D000939:Epitopes; D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; D007518:Isoantibodies; D010446:Peptide Fragments; D014301:Trinitrobenzenes