Regulation of superantigen-induced T cell activation in the absence and the presence of MHC class II.
To study MHC class II-dependent and -independent SAg2 activation and the relative importance of CD80/CD28 costimulation, staphylococcal enterotoxin A (SEA) was presented to T cells as a fusion protein containing the Fab fragment of an mAb directed against the CA215 glycoprotein. Chinese hamster ovary (CHO) cells transfected with HLA-DR4, CA215, and CD80, individually or in combinations, were used as presenting cells. A strong T cell proliferation was obtained when C215Fab-SEA fusion proteins were presented by CHO-DR/CD80 or CHO-CA215/CD80 double transfectants, whereas only low levels of proliferation were seen in the absence of CD80. Large amounts of IL-2, IFN-gamma, and TNF were produced in addition to an increase in IL-2 mRNA as a result of CD80 costimulation. Only approximately 50% of the SEA-reactive T cells responded by expression of IL-2 receptor chains and by blast formation when activated with SEA in the absence of MHC class II. Reverse transcription-PCR-assisted repertoire analysis of SEA-reactive TCR V beta families showed that the CA215-dependent activation involved an expansion of fewer TCR V beta families compared with MHC class II-dependent activation. One-half of the six analyzed TCR V beta families were expanded independently of class II. This indicates that MHC class II has only a partial influence on the TCR V beta repertoire imprinted by SAg. This finding redefines the role of MHC class II in SAg presentation. It is suggested that MHC class II molecules are selected as SAg-binding molecules mainly as a suitable targeting receptor for professional APC expressing costimulatory molecules such as CD80 and CD86.
Lando
P A
PA
Pharmacia and Upjohn, Lund Research Center, Sweden.
Olsson
C
C
Kalland
T
T
Newton
D
D
Kotb
M
M
Dohlsten
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology*; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology*; D018106:CD28 Antigens / Q000235:genetics / Q000276:immunology*; D016466:CHO Cells; D006224:Cricetinae; D004768:Enterotoxins / Q000276:immunology*; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D015804:HLA-DR4 Antigen / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000235:genetics / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology; D018089:Superantigens / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014162:Transfection
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D018122:B7-1 Antigen; D018106:CD28 Antigens; D004768:Enterotoxins; D015804:HLA-DR4 Antigen; D007140:Immunoglobulin Fab Fragments; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011993:Recombinant Fusion Proteins; D018089:Superantigens; C026066:enterotoxin A, Staphylococcal; D007371:Interferon-gamma