TY - JOUR

T1 - Characterization of HIV-Specific CD4+T Cell Responses against Peptides Selected with Broad Population and Pathogen Coverage

A1 - Buggert,Marcus

A1 - Norstrom,Melissa M.

A1 - Czarnecki,Chris

A1 - Tupin,Emmanuel

A1 - Luo,Ma

A1 - Gyllensten,Katarina

A1 - Sonnerborg,Anders

A1 - Lundegaard,Claus

A1 - Lund,Ole

A1 - Nielsen,Morten

A1 - Karlsson,Annika C.

AU - Buggert,Marcus

AU - Norstrom,Melissa M.

AU - Czarnecki,Chris

AU - Tupin,Emmanuel

AU - Luo,Ma

AU - Gyllensten,Katarina

AU - Sonnerborg,Anders

AU - Lundegaard,Claus

AU - Lund,Ole

AU - Nielsen,Morten

AU - Karlsson,Annika C.

PB - Public Library of Science

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

KW - BIOLOGY

KW - CD8(+) T-CELLS

KW - BINDING PREDICTION

KW - ALLELE ASSIGNMENT

KW - CD8-T-CELL MEMORY

KW - CD4-T-CELL HELP

KW - EXON-2 DNA

KW - INFECTION

KW - EPITOPES

KW - GAG

KW - REPLICATION

U2 - 10.1371/journal.pone.0039874

DO - 10.1371/journal.pone.0039874

JO - P L o S One

JF - P L o S One

SN - 1932-6203

IS - 7

VL - 7

ER -