Characterization of HIV-specific CD4+ T cell responses against peptides selected with broad population and pathogen coverage.
CD4+ T cells orchestrate immunity against viral infections, but their importance in HIV infection remains controversial. Nevertheless, comprehensive studies have associated increase in breadth and functional characteristics of HIV-specific CD4+ T cells with decreased viral load. A major challenge fo...
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2012
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oai:doaj.org-article:f199cabb06dd41eb95820c39456e7a3c2021-11-18T07:13:24ZCharacterization of HIV-specific CD4+ T cell responses against peptides selected with broad population and pathogen coverage.1932-620310.1371/journal.pone.0039874https://doaj.org/article/f199cabb06dd41eb95820c39456e7a3c2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22792193/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203CD4+ T cells orchestrate immunity against viral infections, but their importance in HIV infection remains controversial. Nevertheless, comprehensive studies have associated increase in breadth and functional characteristics of HIV-specific CD4+ T cells with decreased viral load. A major challenge for the identification of HIV-specific CD4+ T cells targeting broadly reactive epitopes in populations with diverse ethnic background stems from the vast genomic variation of HIV and the diversity of the host cellular immune system. Here, we describe a novel epitope selection strategy, PopCover, that aims to resolve this challenge, and identify a set of potential HLA class II-restricted HIV epitopes that in concert will provide optimal viral and host coverage. Using this selection strategy, we identified 64 putative epitopes (peptides) located in the Gag, Nef, Env, Pol and Tat protein regions of HIV. In total, 73% of the predicted peptides were found to induce HIV-specific CD4+ T cell responses. The Gag and Nef peptides induced most responses. The vast majority of the peptides (93%) had predicted restriction to the patient's HLA alleles. Interestingly, the viral load in viremic patients was inversely correlated to the number of targeted Gag peptides. In addition, the predicted Gag peptides were found to induce broader polyfunctional CD4+ T cell responses compared to the commonly used Gag-p55 peptide pool. These results demonstrate the power of the PopCover method for the identification of broadly recognized HLA class II-restricted epitopes. All together, selection strategies, such as PopCover, might with success be used for the evaluation of antigen-specific CD4+ T cell responses and design of future vaccines.Marcus BuggertMelissa M NorströmChris CzarneckiEmmanuel TupinMa LuoKatarina GyllenstenAnders SönnerborgClaus LundegaardOle LundMorten NielsenAnnika C KarlssonPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 7, p e39874 (2012) |
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Medicine R Science Q |
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Medicine R Science Q Marcus Buggert Melissa M Norström Chris Czarnecki Emmanuel Tupin Ma Luo Katarina Gyllensten Anders Sönnerborg Claus Lundegaard Ole Lund Morten Nielsen Annika C Karlsson Characterization of HIV-specific CD4+ T cell responses against peptides selected with broad population and pathogen coverage. |
| description |
CD4+ T cells orchestrate immunity against viral infections, but their importance in HIV infection remains controversial. Nevertheless, comprehensive studies have associated increase in breadth and functional characteristics of HIV-specific CD4+ T cells with decreased viral load. A major challenge for the identification of HIV-specific CD4+ T cells targeting broadly reactive epitopes in populations with diverse ethnic background stems from the vast genomic variation of HIV and the diversity of the host cellular immune system. Here, we describe a novel epitope selection strategy, PopCover, that aims to resolve this challenge, and identify a set of potential HLA class II-restricted HIV epitopes that in concert will provide optimal viral and host coverage. Using this selection strategy, we identified 64 putative epitopes (peptides) located in the Gag, Nef, Env, Pol and Tat protein regions of HIV. In total, 73% of the predicted peptides were found to induce HIV-specific CD4+ T cell responses. The Gag and Nef peptides induced most responses. The vast majority of the peptides (93%) had predicted restriction to the patient's HLA alleles. Interestingly, the viral load in viremic patients was inversely correlated to the number of targeted Gag peptides. In addition, the predicted Gag peptides were found to induce broader polyfunctional CD4+ T cell responses compared to the commonly used Gag-p55 peptide pool. These results demonstrate the power of the PopCover method for the identification of broadly recognized HLA class II-restricted epitopes. All together, selection strategies, such as PopCover, might with success be used for the evaluation of antigen-specific CD4+ T cell responses and design of future vaccines. |
| format |
article |
| author |
Marcus Buggert Melissa M Norström Chris Czarnecki Emmanuel Tupin Ma Luo Katarina Gyllensten Anders Sönnerborg Claus Lundegaard Ole Lund Morten Nielsen Annika C Karlsson |
| author_facet |
Marcus Buggert Melissa M Norström Chris Czarnecki Emmanuel Tupin Ma Luo Katarina Gyllensten Anders Sönnerborg Claus Lundegaard Ole Lund Morten Nielsen Annika C Karlsson |
| author_sort |
Marcus Buggert |
| title |
Characterization of HIV-specific CD4+ T cell responses against peptides selected with broad population and pathogen coverage. |
| title_short |
Characterization of HIV-specific CD4+ T cell responses against peptides selected with broad population and pathogen coverage. |
| title_full |
Characterization of HIV-specific CD4+ T cell responses against peptides selected with broad population and pathogen coverage. |
| title_fullStr |
Characterization of HIV-specific CD4+ T cell responses against peptides selected with broad population and pathogen coverage. |
| title_full_unstemmed |
Characterization of HIV-specific CD4+ T cell responses against peptides selected with broad population and pathogen coverage. |
| title_sort |
characterization of hiv-specific cd4+ t cell responses against peptides selected with broad population and pathogen coverage. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2012 |
| url |
https://doaj.org/article/f199cabb06dd41eb95820c39456e7a3c |
| work_keys_str_mv |
AT marcusbuggert characterizationofhivspecificcd4tcellresponsesagainstpeptidesselectedwithbroadpopulationandpathogencoverage AT melissamnorstrom characterizationofhivspecificcd4tcellresponsesagainstpeptidesselectedwithbroadpopulationandpathogencoverage AT chrisczarnecki characterizationofhivspecificcd4tcellresponsesagainstpeptidesselectedwithbroadpopulationandpathogencoverage AT emmanueltupin characterizationofhivspecificcd4tcellresponsesagainstpeptidesselectedwithbroadpopulationandpathogencoverage AT maluo characterizationofhivspecificcd4tcellresponsesagainstpeptidesselectedwithbroadpopulationandpathogencoverage AT katarinagyllensten characterizationofhivspecificcd4tcellresponsesagainstpeptidesselectedwithbroadpopulationandpathogencoverage AT anderssonnerborg characterizationofhivspecificcd4tcellresponsesagainstpeptidesselectedwithbroadpopulationandpathogencoverage AT clauslundegaard characterizationofhivspecificcd4tcellresponsesagainstpeptidesselectedwithbroadpopulationandpathogencoverage AT olelund characterizationofhivspecificcd4tcellresponsesagainstpeptidesselectedwithbroadpopulationandpathogencoverage AT mortennielsen characterizationofhivspecificcd4tcellresponsesagainstpeptidesselectedwithbroadpopulationandpathogencoverage AT annikackarlsson characterizationofhivspecificcd4tcellresponsesagainstpeptidesselectedwithbroadpopulationandpathogencoverage |
| _version_ |
1718423827999883264 |