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.