Binding of natural variants of staphylococcal superantigens SEG and SEI to TCR and MCH class II molecules

FERNANDEZ MM, DE MARZI MC, BERGUER P, BURZYN D, LANGLEY RJ, PIAZZON I, MARIUZZA RA, MALCHIODI EL

MOLECULAR IMMUNOLOGY

Pergamon Press

Lugar: England; Año: 2006 vol. 43 p. 927 - 938

0161-5890

SEG and SEI are staphylococcal superantigens (SAgs) identified recently thatbelong to the egc operon and whose genes are in tandem orientation. Only a fewallelic variants of SEG and SEI have been reported. Here we analyzed fourStaphylococcus 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 stimulatesmouse T-cells bearing Vbeta3, 5 and 13, while SEG stimulates Vbeta7 and 9 in thedraining node when inoculated in the footpad. As another member of the SEBsubfamily, SEG also stimulates mouse Vbeta8.1+2. However, the increase inVbeta8.1+2 T-cells observed at day 2 after inoculation reverts to normal valuesat day 4, whereas it remains high at day 4 following inoculation with SEC3 orSSA. T-cell stimulation assays in the mouse and analysis of the putativeVbeta8.2 binding site on SEG, which includes three non-conserved residues,suggest a possibly unique interaction between Vbeta8.2 and SEG. We also analyzedbiochemical and biophysical characteristics of SEI and SEG binding to theircognate human beta chains by surface plasmon resonance, and binding to theHLA-DR1 MHC class II molecule by gel filtration. SEI binds human Vbeta5.2 andVbeta1 with apparent K(D)'s of 23 and 118 microM, respectively; SEG bindsVbeta13.6 with a K(D) of 5 microM. As suggested by sequence homology, SEIrequires Zn2+ for strong binding to DR1, which goes undetected in the presenceof EDTA. SEG and SEI have characteristics such as co-expression, differentinteraction with MHC class II and stimulation of completely different subsets ofhuman and mouse T-cells, which indicate complementary superantigenic activityand suggest an important advantage to staphylococcal strains in producing themboth.