INVESTIGADORES
BERGUER Paula Mercedes
artículos
Título:
Binding of natural variants of staphylococcal superantigens SEG and SEI to TCR and MHC class II molecule.
Autor/es:
FERNÁNDEZ MM, DE MARZI MC, BERGUER P, BURZYN D, LANGLEY RJ, PIAZZON I, MARIUZZA RA, MALCHIODI EL
Revista:
MOLECULAR IMMUNOLOGY
Editorial:
Pergamon Press.
Referencias:
Lugar: Oxford; Año: 2005 vol. 43 p. 927 - 938
ISSN:
0161-5890
Resumen:
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.