The T 4/Leu3 moleculeis a T cell differentiation antigen which has been shown to help in B cell differentiation, to interact with class II major histocompatibility (MHC) antigens on non-T cells, and to form part of the receptor complex for the HTLV-III virus. Although originally believed to be monomorphic, this molecule has recently been shown to manifest a limited polymorphism. It is hypothesized that the cellular function of T cells is dependent on the T4/Leu3 phenotype expressed.
Three specific aims will be addressed. 1) Characterization of the polymorphism within T4/Leu3. Monoclonal antibodies (mAb) will be generated from mice by immunizing with T cells from individuals with known differences at the epitope recognized by mAb OKT4 (T4 epitope). It is anticipated that some of these mAb will recognize other polymorphic epitopes and will be used to screen different individuals for expression of the given epitope. 2) Assessment of in vitro function by T cells expressing different T4/Leu3 phenotypes. T cells expressing different T4/Leu3 phenotypes will be tested for help and suppression in B cell differentiation as well as proliferation in response to recall antigens, mitogens, and autologous and allogeneic MHC antigens. Blocking experiments using mAb directed against different epitopes will be performed to test whether different portions of the T4/Leu3 molecule play important roles for different functions. In addition to test the T4/Leu3-class II MHC antigen interactions, the effects of mAb against class II MHC antigens will be assessed and correlated with T4/Leu3 phenotype. 3) Correlation of T4Leu3 phenotype with susceptibility to systemic lupus erythematosus (SLE). Initial studies have suggested an association between T4 epitope deficiency and development of SLE. Normal individuals, SLE patients, and patients with non-rheumatologic disease will be screened for T4/Leu3 phenotype to confirm these initial observations and to correlate T4/Leu3 phenotype with clinical and serologic manifestations.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Unknown (R23)
Project #
5R23AR036527-03
Application #
3446380
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1986-12-01
Project End
1989-06-30
Budget Start
1987-12-01
Budget End
1989-06-30
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Stohl, W; Tovar, Z; Talal, N (1990) Generation of cytolytic activity with anti-CD3 monoclonal antibodies involves both IL-2-independent and -dependent components. J Immunol 144:3718-25
Stohl, W; Crow, M K (1990) Inhibition by anti-CD2 monoclonal antibodies of anti-CD3-induced T cell-dependent B cell activation. Cell Immunol 130:257-70
Stohl, W; Hofman, F M; Gray, J D (1990) Differential CD3/T cell antigen receptor-mediated IL-2 production in jurkat T cells. Dissociation of IL-2 response from total inositol phosphate and calcium responses. J Immunol 145:1078-87
Shiba, K; Stohl, W; Gray, J D et al. (1990) A novel role for accessory cells in T cell-dependent B cell differentiation. Cell Immunol 127:458-69
Stohl, W; Gottlieb, A B; Reeves, W H (1989) A functionally unique anti-CD3 monoclonal antibody cross-reactive with basal keratinocytes. Cell Immunol 121:247-60
Stohl, W; Linker-Israeli, M (1989) Inhibitory effects of anti-CD2 monoclonal antibodies on interleukin 2 production and interleukin 2 receptor expression in anti-CD3-induced T cell activation. Cell Immunol 120:351-65
Crow, M K; Kushner, B; Jover, J A et al. (1989) Human peripheral blood T helper cell-induced B cell activation results in B cell surface expression of the CD23 (BLAST-2) antigen. Cell Immunol 121:99-112
Sherris, D; Stohl, W; Mayer, L (1989) Characterization of lymphokines mediating B cell growth and differentiation from monoclonal anti-CD3 antibody-stimulated T cells. J Immunol 142:2343-51
Stohl, W; Posnett, D N; Chiorazzi, N (1988) Differential immunomodulation by anti-CD2 monoclonal antibodies of anti-CD3-induced T cell activation: dependence upon the individual anti-CD3 monoclonal antibody used for activation. Cell Immunol 116:73-85
Stohl, W; Cunningham-Rundles, C; Mayer, L (1988) In vitro induction of T cell-dependent B cell differentiation in patients with common varied immunodeficiency. Clin Immunol Immunopathol 49:273-82

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