Determination of tolerance to self E^α peptides by clonal elimination of H-2E reactive t cells and antigen presentation by H-2A molecules

A series of three synthetic peptides spanning H-2E⁺ chain residues (90-110), (110-130), and (130-150) were synthesized and purified. Mice representative of H-2E- (B6, B10, B10.M, B10.Q, B10.S) and H-2E+ (B10.D2, B10.K, B10.RIII) were immunized with individual peptides and lymph node cells challenged in vitro. Both B6 and BIO mice respond to in vitro challenge to peptides (90-110) (cpm 20,000), (110-130) (cpm 40,000), and (130-150) (cpm 60,000). In contrast all H-2E+ haplotypes were unresponsive to all three peptides (cpms <10,000). Furthermore, BIO mice could be rendered hyporesponsive to E£ peptide challenge following expression of an E^k_£ transgene or mating to an H-2E⁺ strain. The H-2A^{dk, f, q, s} alleles were associated with reduced peptide recognition. Furthermore, alteration of the H-2_β,3 chain in bml2 mutant mice resulted in impaired responses to all three peptides. Immunization with synthetic peptides comprising major histocompatibility molecules may yield insights into mechanisms of self-tolerance.