Abstract

The focus of this application is the interaction between peptides and MHC class I molecules and how that interaction shapes subsequent immune responses. This problem will be addressed using peptides whose sequences are based on known T-cell epitopes. These peptides will be improved by altering non-anchor amino-acids and testing for altered binding. These sequences will be altered both by synthesizing new peptides and by selecting improved epitopes from random libraries. Binding will be assessed by evaluation of both on and off rates using binding in vivo to live cells, and in vitro in cell lysates. In addition the thermostability of the peptide-MHC complex will be determined by X-ray crystallography. Afferent immune responses will be measured in normal, and T-cell receptor transgenic mice. Effectiveness will be assessed by changes in antigen specific precursor frequency. These experiments will have important consequences for immunotherapy of cancer, autoimmune disease and synthetic vaccine design.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI020288-17
Application #
6137124
Study Section
Immunobiology Study Section (IMB)
Program Officer
Prasad, Shiv A
Project Start
1983-02-01
Project End
2001-12-31
Budget Start
2000-01-01
Budget End
2000-12-31
Support Year
17
Fiscal Year
2000
Total Cost
$302,965
Indirect Cost

  Institution

Name
University of North Carolina Chapel Hill
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599

  Publications

Wang, Bo; Sharma, Ashawni; Maile, Robert et al. (2002) Peptidic termini play a significant role in TCR recognition. J Immunol 169:3137-45
Wang, B; Norbury, C C; Greenwood, R et al. (2001) Multiple paths for activation of naive CD8+ T cells: CD4-independent help. J Immunol 167:1283-9
Abdel-Motal, U M; Friedline, R; Poligone, B et al. (2001) Dendritic cell vaccination induces cross-reactive cytotoxic T lymphocytes specific for wild-type and natural variant human immunodeficiency virus type 1 epitopes in HLA-A*0201/Kb transgenic mice. Clin Immunol 101:51-8
Cairns, B A; Maile, R; Buchanan, I et al. (2001) CD8(+) T cells express a T-helper 1--like phenotype after burn injury. Surgery 130:210-6
Maile, R; Wang, B; Schooler, W et al. (2001) Antigen-specific modulation of an immune response by in vivo administration of soluble MHC class I tetramers. J Immunol 167:3708-14
Wang, B; Maile, R; Greenwood, R et al. (2000) Naive CD8+ T cells do not require costimulation for proliferation and differentiation into cytotoxic effector cells. J Immunol 164:1216-22
Wu, Y P; McMahon, E; Kraine, M R et al. (2000) Distribution and characterization of GFP(+) donor hematogenous cells in Twitcher mice after bone marrow transplantation. Am J Pathol 156:1849-54
Serody, J S; Collins, E J; Tisch, R M et al. (2000) T cell activity after dendritic cell vaccination is dependent on both the type of antigen and the mode of delivery. J Immunol 164:4961-7
Mylin, L M; Schell, T D; Roberts, D et al. (2000) Quantitation of CD8(+) T-lymphocyte responses to multiple epitopes from simian virus 40 (SV40) large T antigen in C57BL/6 mice immunized with SV40, SV40 T-antigen-transformed cells, or vaccinia virus recombinants expressing full-length T antigen or epitop J Virol 74:6922-34
Batalia, M A; Kirksey, T J; Sharma, A et al. (2000) Class I MHC is stabilized against thermal denaturation by physiological concentrations of NaCl. Biochemistry 39:9030-8

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