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.
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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2003
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| _version_ | 1826275242801102848 |
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| author | Addo, M Yu, X Rathod, A Cohen, D Eldridge, R Strick, D Johnston, M Corcoran, C Wurcel, A Fitzpatrick, C Feeney, M Rodriguez, W Basgoz, N Draenert, R Stone, DR Brander, C Goulder, P Rosenberg, E Altfeld, M Walker, B |
| author_facet | Addo, M Yu, X Rathod, A Cohen, D Eldridge, R Strick, D Johnston, M Corcoran, C Wurcel, A Fitzpatrick, C Feeney, M Rodriguez, W Basgoz, N Draenert, R Stone, DR Brander, C Goulder, P Rosenberg, E Altfeld, M Walker, B |
| author_sort | Addo, M |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T22:55:44Z |
| format | Journal article |
| id | oxford-uuid:604ce00b-e5f2-44cf-bf81-733c769992a0 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:55:44Z |
| publishDate | 2003 |
| record_format | dspace |
| spelling | oxford-uuid:604ce00b-e5f2-44cf-bf81-733c769992a02022-03-26T17:52:38ZComprehensive 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.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:604ce00b-e5f2-44cf-bf81-733c769992a0EnglishSymplectic Elements at Oxford2003Addo, MYu, XRathod, ACohen, DEldridge, RStrick, DJohnston, MCorcoran, CWurcel, AFitzpatrick, CFeeney, MRodriguez, WBasgoz, NDraenert, RStone, DRBrander, CGoulder, PRosenberg, EAltfeld, MWalker, BCellular 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. |
| spellingShingle | Addo, M Yu, X Rathod, A Cohen, D Eldridge, R Strick, D Johnston, M Corcoran, C Wurcel, A Fitzpatrick, C Feeney, M Rodriguez, W Basgoz, N Draenert, R Stone, DR Brander, C Goulder, P Rosenberg, E Altfeld, M Walker, B 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. |
| title | 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. |
| title_full | 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. |
| title_fullStr | 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. |
| title_full_unstemmed | 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. |
| title_short | 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. |
| title_sort | 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 |
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