title: The murine clan V(H) III related 7183, J606 and S107 and DNA4 families commonly encode for binding to a bacterial B cell superantigen.
abstract: Superantigens, by virtue of their unconventional binding interactions with Ag receptors, can simulate a large subset of mature lymphocytes in the repertoire. Recent studies have documented that in vivo exposure to the model bacterial B cell superantigen, Staphylococcal protein A (SpA), induces large scale effects on murine B-cell clonal selection by mechanism(s) that include deletion of supra-clonal sets. While the structural bases for the immunomodulatory properties of several T-cell superantigens have been well characterized, the requirements for murine Fab-binding of SpA remain incompletely defined. To investigate these structural requirements, a series of direct binding and inhibition studies were performed with a large panel of Moabs of diverse variable region gene usage. These studies confirm previous reports that superantigen binding is completely restricted to the products of clan V(H) III-related families, that include the small S107 and J606 families, and we also demonstrated that usage of the related small DNA4 family commonly correlates with weaker binding activity. Furthermore, our results document that genes from the largest clan V(H) III family, 7183, commonly encode for Fab-mediated binding of SpA, while antibodies from five other VH families, J558, Q52, Sm7, VH11 and VH12, did not display Fab-mediated SpA binding activity. By contributing to the essential foundation for understanding of the structural basis for binding interactions, these findings will aid interpretation of evolving observations regarding the clonal fates induced by in vivo B-cell superantigen exposure.
authors.affiliation: The Sam and Rose Stein Institute for Research on Aging and the Theodore Gildred Cancer Center, Department of Medicine, University of California, San Diego, La Jolla 92093, USA.
authors.forename: S
authors.initials: S
authors.lastname: Cary
authors.forename: M
authors.initials: M
authors.lastname: Krishnan
authors.forename: T N
authors.initials: TN
authors.lastname: Marion
authors.forename: G J
authors.initials: GJ
authors.lastname: Silverman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology*; D001665:Binding Sites / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005803:Genes, Immunoglobulin; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics* / Q000378:metabolism*; D007135:Immunoglobulin Variable Region / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D013205:Staphylococcal Protein A / Q000378:metabolism*; D018089:Superantigens / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D013205:Staphylococcal Protein A; D018089:Superantigens