title: Carboxy-terminal residues of major histocompatibility complex class II-associated peptides control the presentation of the bacterial superantigen toxic shock syndrome toxin-1 to T cells.
abstract: Previous studies have shown that the presentation of some bacterial superantigens by major histocompatibility complex (MHC) class II molecules is strongly influenced by class II-associated peptides. For example, presentation of the toxic shock syndrome toxin-1 (TSST-1) superantigen by antigen-processing-defective T2-I-Ab cells (which expresses I-Ab that is either empty or associated with invariant chain-derived peptides) can be strongly enhanced by some, but not other, I-Ab-binding peptides. Here we investigate the contribution of I-Ab-associated peptides in the presentation of TSST-1 to T cells. The data show that overlapping peptides expressing the same core I-Ab-restricted epitope, but with various N and C termini, can differ profoundly in their ability to promote TSST-1 presentation to T cells. Analysis of altered and truncated peptides indicates that residues at the C-terminal end of the peptide have a dramatic effect on TSST-1 presentation. This effect does not involve a cognate interaction between the peptide and the TSST-1 molecule, but appears to depend on the length of the C-terminal region. These data are consistent with crystallographic studies suggesting that TSST-1 may interact with the C-terminal residues of MHC class II-associated peptides. We also examined the capacity of naturally processed peptides to promote TSST-1 binding using a superantigen blocking assay. The data demonstrated that a naturally processed epitope is dominated by peptides that do not promote strong TSST-1 binding to I-Ab. Taken together, these data suggest that TSST-1 binding to MHC class II molecules is controlled by the C-terminal residues of the associated peptide, and that many naturally processed peptide/class II complexes do not present TSST-1 to T cells. Thus, the peptide dependence of TSST-1 binding to class II molecules may significantly reduce the capacity of TSST-1 to stimulate T cells.
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: R
authors.initials: R
authors.lastname: Wen
authors.forename: D R
authors.initials: DR
authors.lastname: Broussard
authors.forename: S
authors.initials: S
authors.lastname: Surman
authors.forename: T L
authors.initials: TL
authors.lastname: Hogg
authors.forename: M A
authors.initials: MA
authors.lastname: Blackman
authors.forename: D L
authors.initials: DL
authors.lastname: Woodland
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology*; D001427:Bacterial Toxins; D004768:Enterotoxins / Q000276:immunology*; D018604:Epitope Mapping; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006825:Hybridomas; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology*; D011485:Protein Binding; D013329:Structure-Activity Relationship; D018089:Superantigens / Q000276:immunology*
chemical_list: D001427:Bacterial Toxins; D004768:Enterotoxins; D000949:Histocompatibility Antigens Class II; D010455:Peptides; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal; C031818:enterotoxin B, staphylococcal