title: Co-dominant restriction by a mixed-haplotype I-A molecule (alpha k beta b) for the lysozyme peptide 52-61 in H-2k x H-2b F1 mice.
abstract: Helper (CD4+) T lymphocytes recognize protein Ag as peptides associated to MHC class II molecules. The polymorphism of class II alpha- and beta-chains has a major influence on the nature of the peptides presented to CD4+ T lymphocytes. For instance, T cell responses in H-2k and H-2b mice are directed at different epitopes of the hen egg lysozyme (HEL) molecule. The current studies were undertaken with the aim of defining the role of mixed haplotype I-A (alpha k beta b and alpha b beta k) molecules in T cell responses to HEL in (H-2k x H-2b)F1 mice, as well as the nature of the immunogenic peptides of HEL recognized in the context of I-A alpha k beta b and I-A alpha b beta k. A series of HEL-reactive T cell lines and hybridomas derived from MHC class II heterozygous (C57BL/6 x C3H F1) mice were established. Their responsiveness to HEL and synthetic HEL peptides was analyzed with the use of L cells transfected with either I-A alpha k beta b or I-A alpha b beta k as APC. Out of 28 clonal T cell hybridomas tested, 13 (46%) only responded to HEL presented by I-A alpha k beta b, 11 (40%) by I-A alpha b beta k (and to a minor extent I-A alpha k beta k), only 4 (14%) were primarily restricted by I-Ak, and none by I-Ab. All the I-A alpha k beta b-restricted T cell hybridomas responded to the HEL peptide 46-61 and to its shorter fragment 52-61, even at concentrations as low as 0.3 nM. As this determinant has been previously defined as immunodominant for I-Ak but not for I-Ab mice, these results suggest a role for the I-A alpha k chain in the selection and immunodominance of HEL 52-61 in H-2k mice. The fine specificity of I-A alpha k beta b-restricted T cell hybridomas for a series of different HEL peptides around the sequence 52 to 61 suggests that peptide 52-61 binds to I-A alpha k beta b with higher affinity than to I-A alpha k beta k. The peptides recognized in the context of I-A alpha b beta k and I-A alpha k beta k were not identified.
authors.affiliation: Institute for Immunology and Genetics, German Cancer Research Center, Heidelberg, FRG.
authors.forename: J
authors.initials: J
authors.lastname: Moreno
authors.forename: L
authors.initials: L
authors.lastname: Adorini
authors.forename: G J
authors.initials: GJ
authors.lastname: Hämmerling
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D004306:Dose-Response Relationship, Immunologic; D005799:Genes, Dominant; D005802:Genes, MHC Class II; D006183:H-2 Antigens / Q000276:immunology*; D006239:Haplotypes; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex; D051379:Mice; D009113:Muramidase / Q000276:immunology*; D010455:Peptides / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; D010455:Peptides; D009113:Muramidase