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 deve loping 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 o n the E alpha chain (residue 78, 78E alpha/E beta or residue 118, 118 E alpha/E beta) to identify a possible role for carbohydrates in thymi c selection and peripheral T cell activation. Striking differences wer e found among these transgenic mice. Although V beta 10(+) T cells wer e selected positively in all three transgenic strains, positive select ion of V beta 7(+) T cells was impaired in 118E alpha/beta transgenic mice. Spleen cells from both strains with mutant E alpha chains showed selective defects in presentation of peptides to particular T cell hy bridomas. In contrast, neither mutation affected presentation of the s uperantigen Mycoplasma arthriditis mitogen. These results demonstrate that alterations in the gly cosylation of class II E alpha chains migh t affect both central and peripheral T cell regulation.