Comprehensive epitope analysis of human immunodeficiency virus type 1 (HIV-1)-specific T-cell responses directed against the entire expressed HIV-1 genome demonstrate broadly directed responses, but no correlation to viral load.

Abstract

Cellular immune responses play a critical role in the control of human immunodeficiency virus type 1 (HIV-1); however, the breadth of these responses at the single-epitope level has not been comprehensively assessed. We therefore screened peripheral blood mononuclear cells (PBMC) from 57 individuals at different stages of HIV-1 infection for virus-specific T-cell responses using a matrix of 504 overlapping peptides spanning all expressed HIV-1 proteins in a gamma interferon-enzyme-linked immunospot (Elispot) assay. HIV-1-specific T-cell responses were detectable in all study subjects, with a median of 14 individual epitopic regions targeted per person (range, 2 to 42), and all 14 HIV-1 protein subunits were recognized. HIV-1 p24-Gag and Nef contained the highest epitope density and were also the most frequently recognized HIV-1 proteins. The total magnitude of the HIV-1-specific response ranged from 280 to 25,860 spot-forming cells (SFC)/10(6) PBMC (median, 4,245) among all study participants. However, the number of epitopic regions targeted, the protein subunits recognized, and the total magnitude of HIV-1-specific responses varied significantly among the tested individuals, with the strongest and broadest responses detectable in individuals with untreated chronic HIV-1 infection. Neither the breadth nor the magnitude of the total HIV-1-specific CD8+-T-cell responses correlated with plasma viral load. We conclude that a peptide matrix-based Elispot assay allows for rapid, sensitive, specific, and efficient assessment of cellular immune responses directed against the entire expressed HIV-1 genome. These data also suggest that the impact of T-cell responses on control of viral replication cannot be explained by the mere quantification of the magnitude and breadth of the CD8+-T-cell response, even if a comprehensive pan-genome screening approach is applied.

• Authors: M M Addo, X G Yu, A Rathod, D Cohen, R L Eldridge, D Strick, M N Johnston, C Corcoran, A G Wurcel, C A Fitzpatrick, M E Feeney, W R Rodriguez, N Basgoz, R Draenert, David R Stone, C Brander, P J R Goulder, E S Rosenberg, M Altfeld, B D Walker
• Journal: Journal of virology (J Virol) Vol. 77 Issue 3 Pg. 2081-92 (Feb 2003) ISSN: 0022-538X [Print] United States
• PMID: 12525643 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Epitopes, T-Lymphocyte
• Gene Products, nef
• HIV Core Protein p24
• Peptide Fragments
• nef Gene Products, Human Immunodeficiency Virus
• Interferon-gamma

Topics

• Acquired Immunodeficiency Syndrome (immunology, virology)
• Amino Acid Sequence
• Epitopes, T-Lymphocyte
• Female
• Gene Products, nef (immunology)
• Genome, Viral
• HIV Core Protein p24 (immunology)
• HIV-1 (immunology)
• Humans
• Interferon-gamma (biosynthesis)
• Male
• Molecular Sequence Data
• Peptide Fragments (immunology)
• T-Lymphocytes (immunology)
• Viral Load
• nef Gene Products, Human Immunodeficiency Virus