The murine clan VHIII related 7183, J606 and S107 and DNA4 families commonly encode for binding to a bacterial B cell superantigen

Superantigens, by virtue of their unconventional binding interactions with Ag receptors, can simulate a large subset of mature lymphocytes in the repe rtoire. Recent studies have documented that in vivo exposure to the model b acterial B cell superantigen, Staphylococcal protein A (SpA), induces large scale effects on murine B-cell clonal selection by mechanism(s) that inclu de deletion of supra-clonal sets. While the structural bases for the immuno modulatory properties of several T-cell superantigens have been well charac terized, 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 o f diverse variable region gene usage. These studies confirm previous report s that superantigen binding is completely restricted to the products of dan V-H III-related families, that include the small S107 and J606 families, a nd we also demonstrated that usage of the related small DNA4 family commonl y correlates with weaker binding activity. Furthermore, our results documen t that genes from the largest dan 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 ac tivity. By contributing to the essential foundation for understanding of th e structural basis for binding interactions, these findings will aid interp retation of evolving observations regarding the clonal fates induced by in vivo B-cell superantigen exposure. (C) 1999 Elsevier Science Ltd. All right s reserved.