Abstract

Major histocompatibility complex (MHC) molecules function in the immune response by presenting antigenic peptides to T cells. Over two-hundred distinct types of human MHC (HLA) molecules are known, each capable of presenting an array of peptides that fit structurally into their binding regions. Peptides that bind well to one HLA type may bind poorly or not at all to another. In order to develop epitope-based vaccines, peptides that bind crossreactively to a large number of HLA types need to be defined. The overall objective of this project is to identify or synthesize antigenic peptides that are capable of binding to a wide range of HLA molecules. This will be done by a) searching for crossreactive peptides among proteins of various pathogens, b) chemically-modifying the crossreactive peptides as required to optimize binding, and c) testing their ability to be recognized by T cells from humans of diverse HLA types. This research should define the binding requirements of peptides for various HLA molecules as well as provide practical information on the design of T cell epitopes for vaccines and clinical monitoring studies.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research and Development Contracts (N01)
Project #
N01AI095362-003
Application #
6359367
Study Section
Project Start
1999-05-01
Project End
2004-04-30
Budget Start
2000-08-30
Budget End
2002-04-30
Support Year
Fiscal Year
2000
Total Cost
$449,373
Indirect Cost

  Institution

Name
Idm Pharma, Inc.
Department
Type
DUNS #
018540968
City
Irvine
State
CA
Country
United States
Zip Code
92618

  Publications

Regis, David P; Dobano, Carlota; Quinones-Olson, Paola et al. (2008) Transcriptionally active PCR for antigen identification and vaccine development: in vitro genome-wide screening and in vivo immunogenicity. Mol Biochem Parasitol 158:32-45
Fonseca, Simone G; Coutinho-Silva, Adriana; Fonseca, Luiz Augusto M et al. (2006) Identification of novel consensus CD4 T-cell epitopes from clade B HIV-1 whole genome that are frequently recognized by HIV-1 infected patients. AIDS 20:2263-73
Sette, Alessandro; Sidney, John; Bui, Huynh-Hoa et al. (2005) Characterization of the peptide-binding specificity of Mamu-A*11 results in the identification of SIV-derived epitopes and interspecies cross-reactivity. Immunogenetics 57:53-68
Fonseca, Simone G; Moins-Teisserenc, Helene; Clave, Emmanuel et al. (2005) Identification of multiple HLA-A*0201-restricted cruzipain and FL-160 CD8+ epitopes recognized by T cells from chronically Trypanosoma cruzi-infected patients. Microbes Infect 7:688-97
Petersen, Troels R; Bettelli, Estelle; Sidney, John et al. (2004) Characterization of MHC- and TCR-binding residues of the myelin oligodendrocyte glycoprotein 38-51 peptide. Eur J Immunol 34:165-73
Kaufmann, Daniel E; Bailey, Paul M; Sidney, John et al. (2004) Comprehensive analysis of human immunodeficiency virus type 1-specific CD4 responses reveals marked immunodominance of gag and nef and the presence of broadly recognized peptides. J Virol 78:4463-77
Loffredo, John T; Sidney, John; Wojewoda, Christina et al. (2004) Identification of seventeen new simian immunodeficiency virus-derived CD8+ T cell epitopes restricted by the high frequency molecule, Mamu-A*02, and potential escape from CTL recognition. J Immunol 173:5064-76
Mizukoshi, Eishiro; Sidney, John; Livingston, Brian et al. (2004) Cellular immune responses to the hepatitis B virus polymerase. J Immunol 173:5863-71
Shoukry, Naglaa H; Sidney, John; Sette, Alessandro et al. (2004) Conserved hierarchy of helper T cell responses in a chimpanzee during primary and secondary hepatitis C virus infections. J Immunol 172:483-92
Friedrich, Thomas C; Dodds, Elizabeth J; Yant, Levi J et al. (2004) Reversion of CTL escape-variant immunodeficiency viruses in vivo. Nat Med 10:275-81

Showing the most recent 10 out of 39 publications