Abstract

The objective of this application is to better understand the role of cytotoxic T lymphocytes in the recognition and destruction of HIV-infected cells. The investigator has particularly focused on the role of major histocompatibility complex encoded class I molecules and their interactions with peptides. He has used the technologies of molecular biology and cellular immunology to devise strategies for improving the peptide epitopes themselves and used a variety of delivery systems in an attempt to improve delivery to cells and to experimental animals. Of particular novelty is the use of transgenic mice to produce cytotoxic responses to HIV encoded proteins, but which use the human MHC peptide binding molecules to better mimic human antigen presentation. These experiments are designed to allow a better understanding and are pointed towards more rational vaccine design and delivery systems.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI029324-07
Application #
2442475
Study Section
AIDS and Related Research Study Section 1 (ARRA)
Project Start
1990-07-01
Project End
2000-06-30
Budget Start
1997-07-01
Budget End
1998-06-30
Support Year
7
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
University of North Carolina Chapel Hill
Department
Microbiology/Immun/Virology
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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