Replacement of N -glycosylation sites on the MHC class II E alpha chain. Effect on thymic selection and peripheral T cell activation.

Abstract

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.