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Journal of Virology, May 2001, p. 4195-4207, Vol. 75, No. 9
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.9.4195-4207.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Identification and Antigenicity of Broadly Cross-Reactive and Conserved Human Immunodeficiency Virus Type 1-Derived Helper T-Lymphocyte Epitopes

Cara C. Wilson,1,* Brent Palmer,1 Scott Southwood,2 John Sidney,2 Yuichiro Higashimoto,3 Ettore Appella,3 Robert Chesnut,2 Alessandro Sette,2 and Brian D. Livingston2

Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado 802621; Epimmune Inc., San Diego, California 921212; and National Cancer Institute, National Institutes of Health, Bethesda, Maryland 208923

Received 2 November 2000/Accepted 6 February 2001

Human immunodeficiency virus (HIV)-specific helper T lymphocytes (HTL) play a key role in the immune control of HIV type 1 (HIV-1) infection, and as such are an important target of potential HIV-1 vaccines. In order to identify HTL epitopes in HIV-1 that might serve as vaccine targets, conserved HIV-1-derived peptides bearing an HLA-DR binding supermotif were tested for binding to a panel of the most representative HLA-DR molecules. Eleven highly cross-reactive binding peptides were identified: three in Gag and eight in Pol. Lymphoproliferative responses to this panel of peptides, as well as to the HIV-1 p24 and p66 proteins, were evaluated with a cohort of 31 HIV-1-infected patients. All 11 peptides were recognized by peripheral blood mononuclear cells from multiple HIV-infected donors. Many of the responsive HIV-infected subjects showed recognition of multiple peptides, indicating that HIV-1-specific T-helper responses may be broadly directed in certain individuals. A strong association existed between recognition of the parental recombinant HIV-1 protein and the corresponding HTL peptides, suggesting that these peptides represent epitopes that are processed and presented during the course of HIV-1 infection. Lastly, responses to the supermotif peptides were mediated by CD4+ T cells and were restricted by major histocompatibility complex class II molecules. The epitopes described herein are potentially important components of HIV-1 therapeutic and prophylactic vaccines.

* Corresponding author. Mailing address: Divisions of Clinical Immunology and Infectious Diseases, University of Colorado Health Sciences Center, Campus Box B-164, 4200 East Ninth Ave., Denver, CO 80262. Phone: (303) 315-6659. Fax: (303) 315-7642. E-mail: Cara.Wilson{at}UCHSC.edu.

Journal of Virology, May 2001, p. 4195-4207, Vol. 75, No. 9
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.9.4195-4207.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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