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 Ak are also impaired in binding and presentation of the superantistaphylococcal enterotoxin A and that HLA-DM transfection corrects this defect. The poor ability of SEA to bind to Ak on DM-deficient cells is somewhat surprising since Ak has a low affinity for CLIP and is not predominantly occupied with CLIP on T2 cells compared to wide-type APC. These data suggest an influence of HLA-DM on the structure or composition of the Ak/peptide complex beyond its role in the release of invariant chain peptides.
Albert
L J
LJ
Department of Immunology, University of Toronto, Ontario, Canada.
Denzin
L K
LK
Ghumman
B
B
Bangia
N
N
Cresswell
P
P
Watts
T H
TH
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology; D004768:Enterotoxins / Q000276:immunology*; D006681:HLA-D Antigens / Q000235:genetics / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D018089:Superantigens / Q000276:immunology*; D014162:Transfection
D000944:Antigens, Differentiation, B-Lymphocyte; D004768:Enterotoxins; C416189:H2-M antigens; D006681:HLA-D Antigens; C084245:HLA-DM antigens; D000949:Histocompatibility Antigens Class II; C111388:I-Ak antigen; D010455:Peptides; D018089:Superantigens; C045084:invariant chain; C026066:enterotoxin A, Staphylococcal