Abstract

The purpose of the project described in this application is to analyze structural bases of B7:CD28/CTLA4 interactions and respective function of CD28 and CTLA4 in late phase of immune responses, namely clonal expansion and effector function of activated T cells. Specifically the following issues will be addressed: 1) Structural basis of B7:CD28/CTLA4 interaction. 2) The possibility of transduction of opposing biological signals by CD28 and CTLA4. 3) The effector function in anti-tumor immunity through the identification of the receptor involved in rejecting B7-bearing tumors in vivo and cytolysis of B7-bearing tumors in vitro. The experiments will employ site directed mutagenesis of B7-1 and the use of CD28 KO mice.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA069091-05
Application #
2895415
Study Section
Experimental Immunology Study Section (EI)
Program Officer
Mccarthy, Susan A
Project Start
1996-07-01
Project End
2000-04-30
Budget Start
1999-05-07
Budget End
2000-04-30
Support Year
5
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
Ohio State University
Department
Pathology
Type
Schools of Medicine
DUNS #
098987217
City
Columbus
State
OH
Country
United States
Zip Code
43210

  Publications

Wang, Yin; Liu, Yan; Wu, Cindy et al. (2006) Epm2a suppresses tumor growth in an immunocompromised host by inhibiting Wnt signaling. Cancer Cell 10:179-90
Kocak, Ergun; Lute, Kenneth; Chang, Xing et al. (2006) Combination therapy with anti-CTL antigen-4 and anti-4-1BB antibodies enhances cancer immunity and reduces autoimmunity. Cancer Res 66:7276-84
Yang, Tianyu; Lapinski, Philip E; Zhao, Haotian et al. (2005) A rare transporter associated with antigen processing polymorphism overpresented in HLAlow colon cancer reveals the functional significance of the signature domain in antigen processing. Clin Cancer Res 11:3614-23
May Jr, Kenneth F; Roychowdhury, Sameek; Bhatt, Darshna et al. (2005) Anti-human CTLA-4 monoclonal antibody promotes T-cell expansion and immunity in a hu-PBL-SCID model: a new method for preclinical screening of costimulatory monoclonal antibodies. Blood 105:1114-20
Zheng, Xincheng; Yin, Lijie; Liu, Yang et al. (2004) Expression of tissue-specific autoantigens in the hematopoietic cells leads to activation-induced cell death of autoreactive T cells in the secondary lymphoid organs. Eur J Immunol 34:3126-34
Luo, Liqun; Chapoval, Andrei I; Flies, Dallas B et al. (2004) B7-H3 enhances tumor immunity in vivo by costimulating rapid clonal expansion of antigen-specific CD8+ cytolytic T cells. J Immunol 173:5445-50
Gao, Jian-Xin; Chang, Xing; Zheng, Xincheng et al. (2004) A new role for CD28 in the survival of autoreactive T cells in the periphery after chronic exposure to autoantigen. Int Immunol 16:1403-9
Gao, Jian-Xin; Liu, Xingluo; Wen, Jing et al. (2003) Differentiation of monocytic cell clones into CD8 alpha+ dendritic cells (DC) suggests that monocytes can be direct precursors for both CD8 alpha+ and CD8 alpha- DC in the mouse. J Immunol 170:5927-35
Liu, Xingluo; Gao, Jian Xin; Wen, Jing et al. (2003) B7DC/PDL2 promotes tumor immunity by a PD-1-independent mechanism. J Exp Med 197:1721-30
Yang, Tianyu; McNally, Beth A; Ferrone, Soldano et al. (2003) A single-nucleotide deletion leads to rapid degradation of TAP-1 mRNA in a melanoma cell line. J Biol Chem 278:15291-6

Showing the most recent 10 out of 26 publications