Major histocompatibility complex class II-associated peptides determine the binding of the superantigen toxic shock syndrome toxin-1.
Superantigens bind to major histocompatibility complex (MHC) class II proteins and interact with variable parts of the T cell antigen receptor (TCR) beta-chain. Cross-linking the TCR with MHC class II molecules on the antigen-presenting cell by the superantigen leads to T cell activation that plays an essential role in pathogenesis. Recent crystallographic data have resolved the structure of the complexes between HLA-DR1 and staphylococcal enterotoxin B (SEB) and toxic shock syndrome toxin-1 (TSST-1), respectively. For TSST-1, these studies have revealed possible contact sites between the superantigen and the HLA-DR1-bound peptide. Here, we show that TSST-1 binding is dependent on the MHC-II-associated peptides by employing variants of T2 mutant cells deficient in loading of peptides to MHC class II molecules as superantigen-presenting cells. On HLA-DR3-transfected T2 cells, presentation of TSST-1, but not SEB, was dependent on HLA-DR3-associated peptides. Thus, although these superantigens can be recognized in the context of multiple MHC class II alleles and isotypes, they clearly bind to specific subsets of MHC molecules displaying appropriate peptides.
von Bonin
A
A
Bernhard-Nocht-Institut for Tropical Medicine, Hamburg, Germany.
Ehrlich
S
S
Malcherek
G
G
Fleischer
B
B
D000595:Amino Acid Sequence; D017951:Antigen Presentation; D001427:Bacterial Toxins; D002051:Burkitt Lymphoma / Q000473:pathology; D004768:Enterotoxins / Q000276:immunology / Q000378:metabolism*; D015803:HLA-DR3 Antigen / Q000276:immunology / Q000378:metabolism*; D015809:HLA-DR7 Antigen / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008213:Lymphocyte Activation; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D018089:Superantigens / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D001427:Bacterial Toxins; D004768:Enterotoxins; D015803:HLA-DR3 Antigen; D015809:HLA-DR7 Antigen; D046911:Macromolecular Substances; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal; C031818:enterotoxin B, staphylococcal