Mycoplasma arthritides superantigen (MAM) is one of several secreted microbial toxins termed superantigens in reference to their potent activation of subsets that share expression of certain TCR V gene products. Dr. Posnett chose to work with MAM because it derives from a microbe that causes an autoimmune-like arthritis in rodents and that can also infect humans. In preliminary studies, a monoclonal antibody (MAb) specific for a TCR V gene product identified a T cell population that was expanded in cultures exposed to MAM. L cells transfected with human DR, but not those transfected with human DQ MHC molecules were able to present MAM to T cell. The current application pursues these results in order to complete the information on MAM-reactive TCR and MHC molecules in human system. The four specific aims are 1) to define all MAM-reactive TCR V gene products, 2) to produce MAb specific for these V gene products, 3) to define MHC isotopes and alleles that may present MAM to MAM-reactive T cells and to determine the contact site(s) for MAM on MHC, and 4) to define the TCR site(s) reactive with the MAM-MHC complex. The latter two aims will require the production of hybrid TCR and MHC molecules by PCR using overlap extension and also site-directed mutagenesis studies. While the functional significance of superantigens is not yet clear, he and others have postulated roles for superagtigens in autoimmunity. It might therefore be useful to understand the exact specificity of a potentially pathogenic superantigen, since vaccines based on the TCR sequences involved could be produced in the future.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI031140-03
Application #
3146177
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Project Start
1991-03-01
Project End
1996-02-29
Budget Start
1993-03-01
Budget End
1994-02-28
Support Year
3
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Weill Medical College of Cornell University
Department
Type
Schools of Medicine
DUNS #
201373169
City
New York
State
NY
Country
United States
Zip Code
10065
Hodtsev, A S; Choi, Y; Spanopoulou, E et al. (1998) Mycoplasma superantigen is a CDR3-dependent ligand for the T cell antigen receptor. J Exp Med 187:319-27
Liao, L; Marinescu, A; Molano, A et al. (1996) TCR binding differs for a bacterial superantigen (SEE) and a viral superantigen (Mtv-9). J Exp Med 184:1471-82
Posnett, D N (1995) Environmental and genetic factors shape the human T-cell receptor repertoire. Ann N Y Acad Sci 756:71-80
Bhardwaj, N; Hodtsev, A S; Nisanian, A et al. (1994) Human T-cell responses to Mycoplasma arthritidis-derived superantigen. Infect Immun 62:135-44
Posnett, D N; Vissinga, C S; Pambuccian, C et al. (1994) Level of human TCRBV3S1 (V beta 3) expression correlates with allelic polymorphism in the spacer region of the recombination signal sequence. J Exp Med 179:1707-11
Posnett, D N; Sinha, R; Kabak, S et al. (1994) Clonal populations of T cells in normal elderly humans: the T cell equivalent to ""benign monoclonal gammapathy"". J Exp Med 179:609-18
Posnett, D N; Hodtsev, A S; Kabak, S et al. (1993) Interaction of Mycoplasma arthritidis superantigen with human T cells. Clin Infect Dis 17 Suppl 1:S170-5
Posnett, D N; Kabak, S; Hodtsev, A S et al. (1993) T-cell antigen receptor V beta subsets are not preferentially deleted in AIDS. AIDS 7:625-31
Li, Y; Wong, A; Szabo, P et al. (1993) Human Tcrb-V6.10 is a pseudogene with Alu repetitive sequences in the promoter region. Immunogenetics 37:347-55
Munoz, G; Posnett, D N; Witkin, S S (1992) Enrichment of gamma delta T lymphocytes in human semen: relation between gamma delta T cell concentration and antisperm antibody status. J Reprod Immunol 22:47-57

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