Binding of natural variants of staphylococcal superantigens SEG and SEI to TCR and MHC class II molecule.

Printer-friendly versionPrinter-friendly versionPDF versionPDF version
TitleBinding of natural variants of staphylococcal superantigens SEG and SEI to TCR and MHC class II molecule.
Publication TypeJournal Article
Year of Publication2006
AuthorsFernández, MM, De Marzi, MC, Berguer, P, Burzyn, D, Langley, RJ, Piazzon, I, Mariuzza, RA, Malchiodi, EL
JournalMol Immunol
Volume43
Issue7
Pagination927-38
Date Published2006 Mar
ISSN0161-5890
KeywordsAmino Acid Sequence, Animals, Binding Sites, Enterotoxins, Histocompatibility Antigens Class II, HLA-DR1 Antigen, Humans, Mice, Molecular Sequence Data, Receptors, Antigen, T-Cell, alpha-beta, Staphylococcus aureus, Superantigens, Surface Plasmon Resonance, T-Lymphocytes
Abstract

SEG and SEI are staphylococcal superantigens (SAgs) identified recently that belong to the egc operon and whose genes are in tandem orientation. Only a few allelic variants of SEG and SEI have been reported. Here we analyzed four Staphylococcus aureus strains with genotypic variation in both SAgs. However, both SAgs retain key residues in their putative TCR and MHC binding sites and, accordingly, their superantigenic properties. Thus, SEI significantly stimulates mouse T-cells bearing Vbeta3, 5 and 13, while SEG stimulates Vbeta7 and 9 in the draining node when inoculated in the footpad. As another member of the SEB subfamily, SEG also stimulates mouse Vbeta8.1+2. However, the increase in Vbeta8.1+2 T-cells observed at day 2 after inoculation reverts to normal values at day 4, whereas it remains high at day 4 following inoculation with SEC3 or SSA. T-cell stimulation assays in the mouse and analysis of the putative Vbeta8.2 binding site on SEG, which includes three non-conserved residues, suggest a possibly unique interaction between Vbeta8.2 and SEG. We also analyzed biochemical and biophysical characteristics of SEI and SEG binding to their cognate human beta chains by surface plasmon resonance, and binding to the HLA-DR1 MHC class II molecule by gel filtration. SEI binds human Vbeta5.2 and Vbeta1 with apparent K(D)'s of 23 and 118 microM, respectively; SEG binds Vbeta13.6 with a K(D) of 5 microM. As suggested by sequence homology, SEI requires Zn2+ for strong binding to DR1, which goes undetected in the presence of EDTA. SEG and SEI have characteristics such as co-expression, different interaction with MHC class II and stimulation of completely different subsets of human and mouse T-cells, which indicate complementary superantigenic activity and suggest an important advantage to staphylococcal strains in producing them both.

DOI10.1016/j.molimm.2005.06.029
Alternate JournalMol. Immunol.
PubMed ID16023209
Grant ListR01 AI49564 / AI / NIAID NIH HHS / United States
R37 AI36900 / AI / NIAID NIH HHS / United States