The presentation of L-tyrosine-azobenzenearsonate by different mouse Ia molecules uses a common agretope.
The T cell response to L-tyrosine-azobenzenearsonate (ABA-tyr) has been studied using T cell lines and clones derived from three different mouse strains, B10.BR, B10.A (5R) and C57B1/6. In all cases, the arsonate group in conjunction with the amino group of tyrosine formed the functional T cell epitope. Molecules without any one or both of these groups are non-stimulatory. The hydrophobic moiety consisting of the azo-linked benzene rings forms the agretope of the molecule, as is evident from competitive inhibition of T cell stimulation by non-stimulatory analogues lacking the epitope. Substitutions on the benzene ring at ortho or meta positions resulted in decreases in ability to compete, indicating the likelihood of steric inhibition of binding of the agretope with the Ia molecule. This pattern was observed for clones and lines restricted by IAk, IAb and IEb/k MHC class II molecules. Peptides from lambda repressor protein, P84-98 and P73-88, showed haplotype specificity in their ability to inhibit ABA-tyr-induced proliferation of T cell clones, BRTC-4 and B6TC, respectively. The binding constants of ABA-tyr analogues were considered to be comparable to those of lambda repressor peptides because equimolar concentrations resulted in similar levels of competition. A cluster of aromatic amino acids on the floor of most MHC class II molecule binding sites might provide strong hydrophobic interaction with azo-linked benzene rings of ABA-tyr, thus accounting for its immunogenicity in all strains of mice studied.
Baskar
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S
Department of Pathology, Tufts University School of Medicine, Boston, MA 02111.
Sunshine
G H
GH
Leskowitz
S
S
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001391:Azo Compounds / Q000276:immunology*; D001667:Binding, Competitive; D002999:Clone Cells; D000939:Epitopes / Q000276:immunology*; D006239:Haplotypes / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000276:immunology; D010132:p-Azobenzenearsonate / Q000031:analogs & derivatives / Q000276:immunology*
D001391:Azo Compounds; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; C000229:tyrosine-4-azobenzenearsonate; D014443:Tyrosine; D010132:p-Azobenzenearsonate