Abstract

The HLA class I molecules are crucial in the recognition by cytolytic T lymphocytes (CTL) of their targets. In virus infected cells, fragments of viral peptides bind to class I molecules and this class I/peptide complex is recognized by CTLs. T cells are important in the clearance of nearly all virus infections. In the experiments proposed here we will examine the binding of HIV encoded peptides to MHC class I molecules, and the relationship between binding and CTL recognition. In addition, we will undertake a detailed analysis of the interaction between HIV peptides and class I products using a combination of peptide synthesis, and saturation mutagenesis of the HLA genes. These experiments will provide important information on the binding of HIV peptides of HLA and lay the groundwork for the development of synthetic vaccines which can take into account the variability of HLA.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI029324-04
Application #
3144080
Study Section
Special Emphasis Panel (ARR (V1))
Project Start
1990-07-01
Project End
1995-04-30
Budget Start
1993-05-01
Budget End
1994-04-30
Support Year
4
Fiscal Year
1993
Total Cost
Indirect Cost

  Institution

Name
University of North Carolina Chapel Hill
Department
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599

  Publications

Garba, Mohammed L; Pilcher, Christopher D; Bingham, Andrea L et al. (2002) HIV antigens can induce TGF-beta(1)-producing immunoregulatory CD8+ T cells. J Immunol 168:2247-54
Betts, M R; Krowka, J F; Kepler, T B et al. (1999) Human immunodeficiency virus type 1-specific cytotoxic T lymphocyte activity is inversely correlated with HIV type 1 viral load in HIV type 1-infected long-term survivors. AIDS Res Hum Retroviruses 15:1219-28
Kirksey, T J; Pogue-Caley, R R; Frelinger, J A et al. (1999) The structural basis for the increased immunogenicity of two HIV-reverse transcriptase peptide variant/class I major histocompatibility complexes. J Biol Chem 274:37259-64
Caley, R R; Peace-Brewer, A L; Matsui, M et al. (1999) Analysis of the mutant HLA-A*0201 heavy chain H74L: impaired TAP-dependent peptide loading. Hum Immunol 60:743-54
Kuhns, J J; Batalia, M A; Yan, S et al. (1999) Poor binding of a HER-2/neu epitope (GP2) to HLA-A2.1 is due to a lack of interactions with the center of the peptide. J Biol Chem 274:36422-7
Zhao, R; Loftus, D J; Appella, E et al. (1999) Structural evidence of T cell xeno-reactivity in the absence of molecular mimicry. J Exp Med 189:359-70
Betts, M R; Krowka, J; Santamaria, C et al. (1997) Cross-clade human immunodeficiency virus (HIV)-specific cytotoxic T-lymphocyte responses in HIV-infected Zambians. J Virol 71:8908-11
Matsui, M; Warburton, R J; Cogswell, P C et al. (1996) Effects of HIV-1 Tat on expression of HLA class I molecules. J Acquir Immune Defic Syndr Hum Retrovirol 11:233-40
Frelinger, J A; McMillan, M (1996) The role of peptide specificity in MHC class I-restricted allogeneic responses. Immunol Rev 154:45-58
Tussey, L G; Rowland-Jones, S; Zheng, T S et al. (1995) Different MHC class I alleles compete for presentation of overlapping viral epitopes. Immunity 3:65-77

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