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

• Published in: Transplantation Vol. 54; no. 5; p. 920
• Main Authors: Krco, C J, Beito, T G, David, C S
• Format: Journal Article
• Language: English
• Published: United States 01-11-1992
• Subjects: Amino Acid Sequence; Animals; Antigen-Presenting Cells - immunology; Clone Cells - immunology; H-2 Antigens - immunology; Immune Tolerance; Mice; Mice, Inbred Strains; Molecular Sequence Data; T-Lymphocytes - immunology
• ISSN: 0041-1337
• DOI: 10.1097/00007890-199211000-00029

A series of three synthetic peptides spanning H-2E alpha k 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 B10 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, B10 mice could be rendered hyporesponsive to E alpha k peptide challenge following expression of an E alpha k transgene or mating to an H-2E+ strain. The H-2Ad,k,f,q,s alleles were associated with reduced peptide recognition. Furthermore, alteration of the H-2A beta chain in bm12 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.