Immunodominant HIV-1 Cd4+ T cell epitopes in chronic untreated clade C HIV-1 infection.
A dominance of Gag-specific CD8+ T cell responses is significantly associated with a lower viral load in individuals with chronic, untreated clade C human immunodeficiency virus type 1 (HIV-1) infection. This association has not been investigated in terms of Gag-specific CD4+ T cell responses, nor h...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2009-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2661367?pdf=render |
| _version_ | 1819051985420156928 |
|---|---|
| author | Danni Ramduth Cheryl L Day Christina F Thobakgale Nompumelelo P Mkhwanazi Chantal de Pierres Sharon Reddy Mary van der Stok Zenele Mncube Kriebashne Nair Eshia S Moodley Daniel E Kaufmann Hendrik Streeck Hoosen M Coovadia Photini Kiepiela Philip J R Goulder Bruce D Walker |
| author_facet | Danni Ramduth Cheryl L Day Christina F Thobakgale Nompumelelo P Mkhwanazi Chantal de Pierres Sharon Reddy Mary van der Stok Zenele Mncube Kriebashne Nair Eshia S Moodley Daniel E Kaufmann Hendrik Streeck Hoosen M Coovadia Photini Kiepiela Philip J R Goulder Bruce D Walker |
| author_sort | Danni Ramduth |
| collection | DOAJ |
| description | A dominance of Gag-specific CD8+ T cell responses is significantly associated with a lower viral load in individuals with chronic, untreated clade C human immunodeficiency virus type 1 (HIV-1) infection. This association has not been investigated in terms of Gag-specific CD4+ T cell responses, nor have clade C HIV-1-specific CD4+ T cell epitopes, likely a vital component of an effective global HIV-1 vaccine, been identified.Intracellular cytokine staining was conducted on 373 subjects with chronic, untreated clade C infection to assess interferon-gamma (IFN-gamma) responses by CD4+ T cells to pooled Gag peptides and to determine their association with viral load and CD4 count. Gag-specific IFN-gamma-producing CD4+ T cell responses were detected in 261/373 (70%) subjects, with the Gag responders having a significantly lower viral load and higher CD4 count than those with no detectable Gag response (p<0.0001 for both parameters). To identify individual peptides targeted by HIV-1-specific CD4+ T cells, separate ELISPOT screening was conducted on CD8-depleted PBMCs from 32 chronically infected untreated subjects, using pools of overlapping peptides that spanned the entire HIV-1 clade C consensus sequence, and reconfirmed by flow cytometry to be CD4+ mediated. The ELISPOT screening identified 33 CD4+ peptides targeted by 18/32 patients (56%), with 27 of the 33 peptides located in the Gag region. Although the breadth of the CD4+ responses correlated inversely with viral load (p = 0.015), the magnitude of the response was not significantly associated with viral load.These data indicate that in chronic untreated clade C HIV-1 infection, IFN-gamma-secreting Gag-specific CD4+ T cell responses are immunodominant, directed at multiple distinct epitopes, and associated with viral control. |
| first_indexed | 2024-12-21T12:12:38Z |
| format | Article |
| id | doaj.art-ee88e71953b84f48aebb816035d8099c |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T12:12:38Z |
| publishDate | 2009-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-ee88e71953b84f48aebb816035d8099c2022-12-21T19:04:32ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-01-0144e501310.1371/journal.pone.0005013Immunodominant HIV-1 Cd4+ T cell epitopes in chronic untreated clade C HIV-1 infection.Danni RamduthCheryl L DayChristina F ThobakgaleNompumelelo P MkhwanaziChantal de PierresSharon ReddyMary van der StokZenele MncubeKriebashne NairEshia S MoodleyDaniel E KaufmannHendrik StreeckHoosen M CoovadiaPhotini KiepielaPhilip J R GoulderBruce D WalkerA dominance of Gag-specific CD8+ T cell responses is significantly associated with a lower viral load in individuals with chronic, untreated clade C human immunodeficiency virus type 1 (HIV-1) infection. This association has not been investigated in terms of Gag-specific CD4+ T cell responses, nor have clade C HIV-1-specific CD4+ T cell epitopes, likely a vital component of an effective global HIV-1 vaccine, been identified.Intracellular cytokine staining was conducted on 373 subjects with chronic, untreated clade C infection to assess interferon-gamma (IFN-gamma) responses by CD4+ T cells to pooled Gag peptides and to determine their association with viral load and CD4 count. Gag-specific IFN-gamma-producing CD4+ T cell responses were detected in 261/373 (70%) subjects, with the Gag responders having a significantly lower viral load and higher CD4 count than those with no detectable Gag response (p<0.0001 for both parameters). To identify individual peptides targeted by HIV-1-specific CD4+ T cells, separate ELISPOT screening was conducted on CD8-depleted PBMCs from 32 chronically infected untreated subjects, using pools of overlapping peptides that spanned the entire HIV-1 clade C consensus sequence, and reconfirmed by flow cytometry to be CD4+ mediated. The ELISPOT screening identified 33 CD4+ peptides targeted by 18/32 patients (56%), with 27 of the 33 peptides located in the Gag region. Although the breadth of the CD4+ responses correlated inversely with viral load (p = 0.015), the magnitude of the response was not significantly associated with viral load.These data indicate that in chronic untreated clade C HIV-1 infection, IFN-gamma-secreting Gag-specific CD4+ T cell responses are immunodominant, directed at multiple distinct epitopes, and associated with viral control.http://europepmc.org/articles/PMC2661367?pdf=render |
| spellingShingle | Danni Ramduth Cheryl L Day Christina F Thobakgale Nompumelelo P Mkhwanazi Chantal de Pierres Sharon Reddy Mary van der Stok Zenele Mncube Kriebashne Nair Eshia S Moodley Daniel E Kaufmann Hendrik Streeck Hoosen M Coovadia Photini Kiepiela Philip J R Goulder Bruce D Walker Immunodominant HIV-1 Cd4+ T cell epitopes in chronic untreated clade C HIV-1 infection. PLoS ONE |
| title | Immunodominant HIV-1 Cd4+ T cell epitopes in chronic untreated clade C HIV-1 infection. |
| title_full | Immunodominant HIV-1 Cd4+ T cell epitopes in chronic untreated clade C HIV-1 infection. |
| title_fullStr | Immunodominant HIV-1 Cd4+ T cell epitopes in chronic untreated clade C HIV-1 infection. |
| title_full_unstemmed | Immunodominant HIV-1 Cd4+ T cell epitopes in chronic untreated clade C HIV-1 infection. |
| title_short | Immunodominant HIV-1 Cd4+ T cell epitopes in chronic untreated clade C HIV-1 infection. |
| title_sort | immunodominant hiv 1 cd4 t cell epitopes in chronic untreated clade c hiv 1 infection |
| url | http://europepmc.org/articles/PMC2661367?pdf=render |
| work_keys_str_mv | AT danniramduth immunodominanthiv1cd4tcellepitopesinchronicuntreatedcladechiv1infection AT cheryllday immunodominanthiv1cd4tcellepitopesinchronicuntreatedcladechiv1infection AT christinafthobakgale immunodominanthiv1cd4tcellepitopesinchronicuntreatedcladechiv1infection AT nompumelelopmkhwanazi immunodominanthiv1cd4tcellepitopesinchronicuntreatedcladechiv1infection AT chantaldepierres immunodominanthiv1cd4tcellepitopesinchronicuntreatedcladechiv1infection AT sharonreddy immunodominanthiv1cd4tcellepitopesinchronicuntreatedcladechiv1infection AT maryvanderstok immunodominanthiv1cd4tcellepitopesinchronicuntreatedcladechiv1infection AT zenelemncube immunodominanthiv1cd4tcellepitopesinchronicuntreatedcladechiv1infection AT kriebashnenair immunodominanthiv1cd4tcellepitopesinchronicuntreatedcladechiv1infection AT eshiasmoodley immunodominanthiv1cd4tcellepitopesinchronicuntreatedcladechiv1infection AT danielekaufmann immunodominanthiv1cd4tcellepitopesinchronicuntreatedcladechiv1infection AT hendrikstreeck immunodominanthiv1cd4tcellepitopesinchronicuntreatedcladechiv1infection AT hoosenmcoovadia immunodominanthiv1cd4tcellepitopesinchronicuntreatedcladechiv1infection AT photinikiepiela immunodominanthiv1cd4tcellepitopesinchronicuntreatedcladechiv1infection AT philipjrgoulder immunodominanthiv1cd4tcellepitopesinchronicuntreatedcladechiv1infection AT brucedwalker immunodominanthiv1cd4tcellepitopesinchronicuntreatedcladechiv1infection |