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

被引:21
作者
Buggert, Marcus [1 ]
Norstrom, Melissa M. [1 ]
Czarnecki, Chris [2 ]
Tupin, Emmanuel [3 ]
Luo, Ma [2 ,4 ]
Gyllensten, Katarina [5 ]
Sonnerborg, Anders [1 ,6 ]
Lundegaard, Claus [7 ]
Lund, Ole [7 ]
Nielsen, Morten [7 ]
Karlsson, Annika C. [1 ]
机构
[1] Karolinska Inst, Dept Lab Med, Div Clin Microbiol, Stockholm, Sweden
[2] Publ Hlth Agcy Canada, Natl Microbiol Lab, Winnipeg, MB, Canada
[3] Swedish Inst Infect Dis Control, Dept Virol, Stockholm, Sweden
[4] Univ Manitoba, Dept Med Microbiol, Winnipeg, MB, Canada
[5] Stockholm S Gen Hosp Sodersjukhuset, Gay Mens Hlth Clin, Stockholm, Sweden
[6] Karolinska Inst, Dept Med Huddinge, Div Infect Dis, Stockholm, Sweden
[7] Tech Univ Denmark, Dept Syst Biol, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark
来源
PLOS ONE | 2012年 / 7卷 / 07期
基金
瑞典研究理事会;
关键词
CD8(+) T-CELLS; EXON-2; DNA; EPITOPES; GAG; INFECTION; REPLICATION; VACCINATION; IMMUNITY; MEMORY;
D O I
10.1371/journal.pone.0039874
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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页数:10
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