T-CELL EPITOPE SELECTION - DOMINANCE MAY BE DETERMINED BY BOTH AFFINITY FOR MAJOR HISTOCOMPATIBILITY COMPLEX AND STOICHIOMETRY OF EPITOPE

The majority of T cell hybridomas produced in the BALB/c mouse in response to immunization with lambda-repressor cI recognize a peptide fragment comprising of residues 12 to 26 (P12-26). Some other parts of the cI (P1-14. P33-48 and P73-88) are defective in generating T cell responses in the BAL/c mouse. P73-88 may be converted into a T cell determinant if a few more amino acid residues are included (P67-88). Together with P46-67 and P80-102, most peptides derived from cI were capable of eliciting T cell responses by themselves in BAL/c mouse. The mechanisms underlying the selection of P12-26 over the other epitopes when lambda-repressor was used as immunogen were examined. The dominant response to P12-26 was attenuated by tolerizing with intravenous administration of P12-26. Under such treatment the T cell response to P12-26 was reduced by 80 % but there was no enhancement on the responses toward other epitopes. The selection of P12-26 is. thus, unlikely to be due to a competition at the T cell level. It was also found that the dominance of P12-26 was not simply due to a higher affinity of P12-26 for major histocompatibility complex molecules. For example P12-26 binds better to I-A(d) molecule than P80-102, but co-injection with equimole of P12-26 only slightly inhibited P80-102-induced T cell response. Instead, it required a few molar excess of P12-26 to effectively block the association of P80-102 with I-A(d) molecules and to inhibit the T cell immunity to P80-102. Since epitopes such as P46-67, P67-88 and P80-102 were generated from lambda-repressor cI at a lower molar basis than that of P12-26, it is suggested that the dominance of P12-26 was probably generated by such stoichiometry difference, in addition to the higher affinity of P12-26 for I-A(d) molecules.