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 Ek£ transgene or mating to an H-2E+ strain. The H-2Adk, f, q, s alleles were associated with reduced peptide recognition. Furthermore, alteration of the H-2β,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.
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