Definintion of antigen specific receptors on human T lymphocytes has been hampered by the extraordinary heterogeneity of these cells and the MHC restrictions which govern their activation. However, the recent development of clonal populations of antigen specific IL-2 dependent T cells and the availability of multiple monoclonal antibodies to T lineage specific surface glycoproteins make it possible to overcome these difficulties. To this end, we will examine the capacity of various monoclonal antibodies to indluence antigen spcific recognition and effector function of homogeneous T cell populations in the absence of complement. These will include monoclonal antibodies to nonpolymorphic determinants found on all mature T lymphocytes (anti-T1, T3, T3A, T3B, T11, T12), monoclonal antibodies to nonpolymorphic determinants selectively expressed on subsets of T cells (anti-T4, T4A, T4B, T4C, T8, T8A, T8B, T8C, etc.) and monoclonal antibodies to clonotypic (anti-idiotypic) determinants unique to individual clones. Utilizing cytotoxic T4 and T8 clones with defined MHC class II and class I target specificities, respectively, and noncytotoxic soluble antigen (KLH) specific clones we will define: 1) T cell surface molecules required for the recognition phase of CTL effector function in comparison with those employed in antigen specific recognition by noncytolytic clones; 2) the relationship of T cell function to the novel 20KD glycoprotein defined by anti-T3 antibodies which rapidly induce its modulation via external shedding; 3) the potential antigen binding properties of 35S-labelled T3 molecules and any comodulating structures; 4) the effect of clonotypic antibodies on enhancing or inhibiting function and growth of clonotype positive and negative clones, frequency and specificity of such clones, the relationship of structures defined by clonotypic antibodies and nonpolymorphic structures detected with anti-T3, anti-T4 and anti-T8, and the nature of the cellular clonal anti-clonal response; and 5) activation antigens expressed by one or another T celll subset, the relationship of activation structures to clonal function, and possible genetic polymorphism of these molecules.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI019807-05
Application #
3129236
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1983-05-01
Project End
1988-04-30
Budget Start
1987-05-01
Budget End
1988-04-30
Support Year
5
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02115
Mallis, Robert J; Arthanari, Haribabu; Lang, Matthew J et al. (2018) NMR-directed design of pre-TCR? and pMHC molecules implies a distinct geometry for pre-TCR relative to ??TCR recognition of pMHC. J Biol Chem 293:754-766
Mallis, Robert J; Reinherz, Ellis L; Wagner, Gerhard et al. (2016) Backbone resonance assignment of N15, N30 and D10 T cell receptor ? subunits. Biomol NMR Assign 10:35-9
Reinherz, Ellis L; Wang, Jia-huai (2015) Codification of bidentate pMHC interaction with TCR and its co-receptor. Trends Immunol 36:300-6
Mallis, Robert J; Bai, Ke; Arthanari, Haribabu et al. (2015) Pre-TCR ligand binding impacts thymocyte development before ??TCR expression. Proc Natl Acad Sci U S A 112:8373-8
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Choi, Young I; Duke-Cohan, Jonathan S; Tan, Jing et al. (2013) Plxnd1 expression in thymocytes regulates their intrathymic migration while that in thymic endothelium impacts medullary topology. Front Immunol 4:392
Touma, Maki; Keskin, Derin B; Shiroki, Fumiko et al. (2011) Impaired B cell development and function in the absence of IkappaBNS. J Immunol 187:3942-52
Kim, Sun Taek; Touma, Maki; Takeuchi, Koh et al. (2010) Distinctive CD3 heterodimeric ectodomain topologies maximize antigen-triggered activation of alpha beta T cell receptors. J Immunol 185:2951-9
Vernier, Gregory; Wang, Jie; Jennings, Laura D et al. (2009) Solubilization and characterization of the anthrax toxin pore in detergent micelles. Protein Sci 18:1882-95
Kim, Sun Taek; Takeuchi, Koh; Sun, Zhen-Yu J et al. (2009) The alphabeta T cell receptor is an anisotropic mechanosensor. J Biol Chem 284:31028-37

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