Quantitative defect in staphylococcal enterotoxin A binding and presentation by HLA-DM-deficient T2.Ak cells corrected by transfection of HLA-DM genes

HLA-DM facilitates peptide acquisition by MHC class II proteins within the endosomes of APC by facilitating release of invariant chain peptide intermediates (CLIP) from the class II molecules. T2 cells have a deletion in the MHC II region which deletes HLA-DM and MHC II genes. T2 cells transfected with MHC class II proteins are defective in protein presentation, a defect that is corrected by HLA-DM transfection. Here we show that T2 cells transfected with A(k) are also impaired in binding and presentation of the superantigen staphyococcal enterotoxin A and that HLA-DM transfection corrects this defect. The poor ability of SEA to bind to A(k) on DM-deficient cells is somewhat surprising since A(k) has a low affinity for CLIP and is not predominantly occupied with CLIP on T2 cells compared to wild-type APC. These data suggest an influence of HLA-DM on the structure or composition of the A(k)/peptide complex beyond its role in the release of invariant chain peptides. (C) 1998 Academic Press.