Epitope-specific regulation of the T cell repertoire: carrier recognition in association with I-E or I-A does not influence the restriction of hapten-specific T cells.
The T cell repertoire of BALB/c mice contains clones capable of recognizing p-azobenzenearsonate (ABA)-tyrosine (Tyr) in association with both I-A and I-E-encoded class II molecules. Immunization of BALB/c animals with ABA-GAT (terpolymer of L-Glu60-L-Ala30-L-Tyr10) or ABA-GLT (terpolymer of L-Glu51-L-Lys34-L-Tyr15) instead of ABA-Tyr reduces the secondary proliferative response to ABA-Tyr in vitro. Limiting dilution experiments indicate that this situation corresponds to the recruitment of fewer ABA-specific T cells in vivo. The same experiments, performed in A.TH mice, which are nonresponder to both GAT and GLT, demonstrate that the number of ABA-specific T cells stimulated in vivo with ABA conjugates depends on the Ir gene-controlled immunogenicity of the carrier rather than on the ABA epitope density on the immunogen. Although GAT is preferentially recognized in association with A, and GLT with E, ABA-GAT and ABA-GLT stimulate both A and E-restricted ABA T cells in vivo and in vitro. The ABA-Tyr-specific T cell repertoire is not qualitatively affected by the carrier. This demonstrates that the inhibition of hapten-specific T cell expression upon immunization with ABA conjugates does not result from a competition between hapten and carrier-specific T cells for epitope recognition in association with the same Ia molecule on antigen-presenting cells.
E
E
Trannoy
D
D
Regnier
H
H
Campbell
M
M
Seman
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology; D000939:Epitopes; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007156:Immunologic Memory; D008264:Macrophages / Q000276:immunology; D008285:Major Histocompatibility Complex; D008297:Male; D051379:Mice; D010455:Peptides / Q000276:immunology; D011108:Polymers; D013601:T-Lymphocytes / Q000276:immunology*; D010132:p-Azobenzenearsonate / Q000276:immunology
D002352:Carrier Proteins; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D010455:Peptides; D011108:Polymers; C022272:glutamic acid-lysine-tyrosine terpolymer; C020749:GAT; D010132:p-Azobenzenearsonate