title: Streptococcus pyogenes type 5 M protein is an antigen, not a superantigen, for human T cells.
abstract: M proteins are coiled-coil dimers expressed on group A streptococcal cell surfaces. They have an important role in host antistreptococcal immunity and in poststreptococcal autoimmune sequelae. Controversy has arisen regarding whether type 5 M proteins are superantigenic for human T cells. To investigate this, we have produced and tested M5 in the form of two novel recombinant proteins. We found no evidence of superantigenicity using either recombinant whole M5 protein (rM5) or recombinant pep M5 protein (rpepM5) to activate peripheral blood mononuclear cells (PBMC) from healthy adult volunteers. Short-term, rM5-specific T-cell lines from different subjects were uniformly self-APC restricted and showed no consistent pattern of TCR V beta usage. A synthetic peptide of M5 residues 217-237 was found to contain epitope(s) recognized by some rM5-specific human T cells. PBMC responses to rM5 and rpepM5 in 3- and 7-day proliferation assays were characteristic of antigenic rather than superantigenic stimulation. We conclude that type 5 M protein activates human T cells as a conventional antigen.
authors.affiliation: School of Clinical Medical Sciences (Rheumatology), University of Newcastle upon Tyne, United Kingdom.
authors.forename: B
authors.initials: B
authors.lastname: Degnan
authors.forename: J
authors.initials: J
authors.lastname: Taylor
authors.forename: C
authors.initials: C
authors.lastname: Hawkes
authors.forename: U
authors.initials: U
authors.lastname: O'Shea
authors.forename: J
authors.initials: J
authors.lastname: Smith
authors.forename: J H
authors.initials: JH
authors.lastname: Robinson
authors.forename: M A
authors.initials: MA
authors.lastname: Kehoe
authors.forename: A
authors.initials: A
authors.lastname: Boylston
authors.forename: J A
authors.initials: JA
authors.lastname: Goodacre
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins / Q000276:immunology*; D002352:Carrier Proteins; D002460:Cell Line; D006801:Humans; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000276:immunology; D013297:Streptococcus pyogenes / Q000276:immunology*; D018089:Superantigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013745:Tetanus Toxoid / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D000954:Antigens, Surface; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011994:Recombinant Proteins; D018089:Superantigens; D013745:Tetanus Toxoid; C014689:streptococcal M protein