Staphylococcal enterotoxins are the cause of common staphylococcal foodborne intoxication. Several of these enterotoxins are known to have both mitogenic and immunosuppressive activity. We have found that the immunosuppressive activity of staphylococcal enterotoxin B (SEB) is due, at least in part, to the induction of suppressor cells. We have also found that SEB induces multiple suppressor cell populations, distinguishable by cell surface morphology, which appear to co-operate in the regulation of the immune response. We have found, moreover, that at least one of these SEB-induced suppressor cell populations is involved in the inhibition of antibody secretion by the plasmacytoma tumor cell line MOPC-315. In this way we have the unique advantage of being able to employ an established cell line, both as a model for effector cell function (which is senstivie to the suppressor cell activity), as wll as a model for assessing tumor """"""""immunity"""""""" induced by the SEB.
The first aim of this proposal is to assess the interactions both among these suppressor cells populations, and between these regulatory cells and the specific target effector cells within the immune system. We propose specific approaches to determine whether certain of these populations act as suppressor-""""""""inducers"""""""", or - """"""""effectors"""""""", the nature of any genetic restrictions, antigen specificity, and the possible production of any suppressor factors. Our previous work has also shown that functional suppressor cell activity is dependent on prostaglandin synthesis. We propose to determine which of the various individual suppressor cell populations are dependent on prostaglandin synthesis by using various specific inhibitors of arachidonic acid metabolism. The second major goal of these studies is to assess the structural epitope of the SEB which is responsible for the immunosuppressive activity. We propose specific experiments using a combination of peptide fragments and SEB-specific monoclonal antibodies for this analysis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI023828-02
Application #
3136279
Study Section
Bacteriology and Mycology Subcommittee 1 (BM)
Project Start
1987-03-01
Project End
1991-02-28
Budget Start
1988-03-01
Budget End
1989-02-28
Support Year
2
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Temple University
Department
Type
Schools of Medicine
DUNS #
City
Philadelphia
State
PA
Country
United States
Zip Code
19122
Zhang, Lily; Rogers, Thomas J (2013) Assessment of the functional regions of the superantigen staphylococcal enterotoxin B. Toxins (Basel) 5:1859-71
Cornwell, W D; Rogers, T J (1999) Role of interleukin-2 in superantigen-induced T-cell anergy. Immunology 96:193-201
Garcia, C; Briggs, C; Zhang, L et al. (1998) Molecular characterization of the putative T-cell receptor cavity of the superantigen staphylococcal enterotoxin B. Immunology 94:160-6
Rogers, T J; Zhang, L (1997) Structural basis for the interaction of superantigen with the alternative superantigen-binding receptor p85. Mol Immunol 34:263-72
Briggs, C; Garcia, C; Zhang, L et al. (1997) Mutations affecting the superantigen activity of staphylococcal enterotoxin B. Immunology 90:169-75
Rogers, T J; Guan, L; Zhang, L (1995) Characterization of an alternative superantigen binding site expressed on a renal fibroblast cell line. Int Immunol 7:1721-7
Taub, D D; Rogers, T J (1992) Direct activation of murine T cells by staphylococcal enterotoxins. Cell Immunol 140:267-81
Binek, M; Newcomb, J R; Rogers, C M et al. (1992) Localisation of the mitogenic epitope of staphylococcal enterotoxin B. J Med Microbiol 36:156-63
Taub, D D; Newcomb, J R; Rogers, T J (1992) Effect of isotypic and allotypic variations of MHC class II molecules on staphylococcal enterotoxin presentation to murine T cells. Cell Immunol 141:263-78
Lin, Y S; Hu, S C; Jan, M S et al. (1991) Inhibition of the delayed-type hypersensitivity response by staphylococcal enterotoxin B-induced suppressor T cells. Cell Immunol 132:532-8

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