Staphylococcal enterotoxin A induces small clusters of HLA-DR1 on B cells.
The superantigen SEA causes non-specific hyperactivation of T and B cells at low concentrations. Studies of mutants or soluble proteins suggest SEA is bivalent for its ligand, MHC class II. However, the interaction between these molecules on intact cells is unknown. On primary mouse B cells expressing the MHC class II allele HLA-DR1, measurements of Förster Resonance Energy Transfer between HLA-DR1 molecules on SEA-treated cells indicated specific clustering, not observed in untreated or monovalent superantigen treated cells. Tomographic visualization and electron microscopy of immunogold-labeled SEA-treated B cells revealed small clusters of surface HLA-DR1 (< or = 4 gold labels). These results present direct visual evidence of SEA-mediated clustering of MHC class II molecules on treated antigen presenting cells, and provide a new structural approach to addressing problems of this nature.
Narayan
Kedar
K
Graduate Program in Immunology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
Perkins
Edward M
EM
Murphy
Gavin E
GE
Dalai
Sarat K
SK
Edidin
Michael
M
Subramaniam
Sriram
S
Sadegh-Nasseri
Scheherazade
S
D000483:Alleles; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D004591:Electrophoresis, Polyacrylamide Gel; D004768:Enterotoxins / Q000494:pharmacology*; D031541:Fluorescence Resonance Energy Transfer; D015798:HLA-DR1 Antigen / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D020349:Surface Plasmon Resonance
D004768:Enterotoxins; D015798:HLA-DR1 Antigen; C026066:enterotoxin A, Staphylococcal