Abstract

As a result of their clonal origin, lymphoid tumors present as tumor-specific antigens unique cell surface epitopes related their recognition structures. We have produced lymphoma-specific monoclonal antibodies and demonstrated that the target structure, a disulfide-bonded heterodimer, is the T cell antigen specific receptor. Nearest-neighbor analysis of the receptor using chemical cross-linkers demonstrated that the receptor is part of a multichain complex. Recently, we have identified another heterodimer on the surface of T lymphoma cells. This molecule is serologically distinct from the alpha/beta antigen receptor and may represent a new family of T cell specific cell surface molecule. Our current goals are (1) to use conventional methods and recombinant DNA technology to produce additional antibodies to the components of the T cell receptor complex, (2) to evaluate their efficacy in specific immunotherapy, and (3) to further characterize the novel T cell heterodimer and determine its relationship to the T cell antigen receptor.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37CA040041-06
Application #
3482458
Study Section
Experimental Immunology Study Section (EI)
Project Start
1985-01-01
Project End
1991-03-31
Budget Start
1989-04-01
Budget End
1990-03-31
Support Year
6
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
University of California Berkeley
Department
Type
Schools of Arts and Sciences
DUNS #
094878337
City
Berkeley
State
CA
Country
United States
Zip Code
94704

  Publications

Wei, Joyce; Loke, P'ng; Zang, Xingxing et al. (2011) Tissue-specific expression of B7x protects from CD4 T cell-mediated autoimmunity. J Exp Med 208:1683-94
Pentcheva-Hoang, Tsvetelina; Chen, Lieping; Pardoll, Drew M et al. (2007) Programmed death-1 concentration at the immunological synapse is determined by ligand affinity and availability. Proc Natl Acad Sci U S A 104:17765-70
Pentcheva-Hoang, Tsvetelina; Egen, Jackson G; Wojnoonski, Kathleen et al. (2004) B7-1 and B7-2 selectively recruit CTLA-4 and CD28 to the immunological synapse. Immunity 21:401-13
Stohl, William; Xu, Dong; Kim, Kyoung Soo et al. (2004) MHC class II-independent and -dependent T cell expansion and B cell hyperactivity in vivo in mice deficient in CD152 (CTLA-4). Int Immunol 16:895-904
Zang, Xingxing; Loke, P'ng; Kim, Jayon et al. (2003) B7x: a widely expressed B7 family member that inhibits T cell activation. Proc Natl Acad Sci U S A 100:10388-92
Egen, Jackson G; Allison, James P (2002) Cytotoxic T lymphocyte antigen-4 accumulation in the immunological synapse is regulated by TCR signal strength. Immunity 16:23-35
Egen, Jackson G; Kuhns, Michael S; Allison, James P (2002) CTLA-4: new insights into its biological function and use in tumor immunotherapy. Nat Immunol 3:611-8
Hurwitz, Arthur A; Sullivan, Timothy J; Sobel, Raymond A et al. (2002) Cytotoxic T lymphocyte antigen-4 (CTLA-4) limits the expansion of encephalitogenic T cells in experimental autoimmune encephalomyelitis (EAE)-resistant BALB/c mice. Proc Natl Acad Sci U S A 99:3013-7
Sullivan, T J; Letterio, J J; van Elsas, A et al. (2001) Lack of a role for transforming growth factor-beta in cytotoxic T lymphocyte antigen-4-mediated inhibition of T cell activation. Proc Natl Acad Sci U S A 98:2587-92
Cassell, D J (2001) Validity of the two-signal model for activation of CD28-deficient T lymphocytes: quantitative characterization of an alternative costimulatory function of dendritic cells. Scand J Immunol 53:346-56

Showing the most recent 10 out of 51 publications