Recognition of foreign antigens by immune T lymphocytes requires the presentation of short protein segments, termed peptides, bound to major histocompatability complex (MHC) molecules that serve as ligands for T cell receptors. Thousands of peptides, derived from both cellular and pathogen molecules, are presented during an immune response to infection or vaccination, but only a small proportion of these have been characterized. The current project seeks to define in great detail the peptides presented by specific human MHC class I molecules (HLA-A, -B, and ~C). Peptides will be extracted from purified HLA molecules derived from human cell lines both before and after infection by human immunodeficiency virus-1 (HIV-1). Comparative peptide maps will be generated using chromatography and mass spectrometry to separate and sequence the released peptides. This approach will provide extensive information on the potential target epitopes available to HLA-restricted human T cells responding to HIV. A searchable T cell ligand database will be developed as a comprehensive source of information on peptides presented by HLA molecules.

Project Start
1999-05-01
Project End
2004-04-30
Budget Start
2000-09-13
Budget End
2002-04-30
Support Year
Fiscal Year
2000
Total Cost
$360,407
Indirect Cost
Name
University of Oklahoma Health Sciences Center
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
937727907
City
Oklahoma City
State
OK
Country
United States
Zip Code
73117
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Wren, Jonathan D; Hildebrand, William H; Chandrasekaran, Sreedevi et al. (2005) Markov model recognition and classification of DNA/protein sequences within large text databases. Bioinformatics 21:4046-53
Hickman, Heather D; Luis, Angela D; Buchli, Rico et al. (2004) Toward a definition of self: proteomic evaluation of the class I peptide repertoire. J Immunol 172:2944-52
Sathiamurthy, M; Hickman, H D; Cavett, J W et al. (2003) Population of the HLA ligand database. Tissue Antigens 61:12-9
Hildebrand, William H; Turnquist, Heth R; Prilliman, Kiley R et al. (2002) HLA class I polymorphism has a dual impact on ligand binding and chaperone interaction. Hum Immunol 63:248-55
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