Replacement of N-glycosylation sites on the MHC class II E alpha chain. Effect on thymic selection and peripheral T cell activation.
MHC class II molecules play a central role in thymic selection of developing T cells, Ag presentation to immunocompetent CD4+ T cells, and T cell activation by superantigens. We have established transgenic A.CA mice expressing either the wild-type E alpha d molecule (E alpha/E beta), or an E alpha d molecule altered at an N-glycosylation site on the E alpha chain (residue 78, 78E alpha/E beta or residue 118, 118E alpha/E beta) to identify a possible role for carbohydrates in thymic selection and peripheral T cell activation. Striking differences were found among these transgenic mice. Although V beta 10+ T cells were selected positively in all three transgenic strains, positive selection of V beta 7+ T cells was impaired in 118E alpha/E beta transgenic mice. Spleen cells from both strains with mutant E alpha chains showed selective defects in presentation of peptides to particular T cell hybridomas. In contrast, neither mutation affected presentation of the superantigen Mycoplasma arthriditis mitogen. These results demonstrate that alterations in the glycosylation of class II E alpha chains might affect both central and peripheral T cell regulation.
Ishikawa
S
S
Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Kowal
C
C
Cole
B
B
Thomson
C
C
Diamond
B
B
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D001483:Base Sequence; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D005260:Female; D005434:Flow Cytometry; D006031:Glycosylation; D000949:Histocompatibility Antigens Class II / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008805:Mice, Inbred A; D008822:Mice, Transgenic; D008845:Microinjections; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010455:Peptides / Q000276:immunology; D013329:Structure-Activity Relationship; D018089:Superantigens / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*
D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D010455:Peptides; D018089:Superantigens