CD4+T cells from HIV-1-infected patients recognize wild-type and mutant human immunodeficiency virus-1 protease epitopes

被引:0
作者
Muller, N. G. [4 ]
Alencar, R. [5 ]
Jamal, L. [5 ]
Hammer, J. [7 ]
Sidney, J. [8 ]
Sette, A. [8 ]
Brindeiro, R. M. [6 ]
Kalil, J. [2 ,4 ]
Cunha-Neto, E. [1 ,2 ,4 ]
Moraes, S. L. [3 ,4 ]
机构
[1] Univ Sao Paulo, Lab Clin Immunol & Allergy LIM 60, Sch Med, Div Clin Immunol & Allergy,Dept Med, BR-01246000 Sao Paulo, Brazil
[2] Univ Sao Paulo, Heart Inst InCor, BR-01246000 Sao Paulo, Brazil
[3] Univ Sao Paulo, Inst Trop Med, BR-01246000 Sao Paulo, Brazil
[4] Natl Inst Sci & Technol, Inst Invest Immunol, Sao Paulo, Brazil
[5] Ctr Training Sexually Transmitted Dis & AIDS, Sao Paulo, Brazil
[6] Univ Fed Rio de Janeiro, Mol Virol Lab, Inst Biol, Rio De Janeiro, Brazil
[7] Hoffmann La Roche Inc, Dept Genom & Informat Sci, Nutley, NJ 07110 USA
[8] La Jolla Inst Allergy & Immunol, San Diego, CA USA
基金
巴西圣保罗研究基金会; 美国国家卫生研究院;
关键词
antigens; epitopes; CD4 T cells (T helper; Th0; Th1; Th2; Th3; Th17); flow cytometry; FACS; human immunodeficiency virus (AIDS; HIV-1; HIV-2); proliferation; CD4(+) T-CELLS; IMMUNE-RESPONSES; HIV-1; IDENTIFICATION; INFECTION; VIREMIA; INDIVIDUALS; FREQUENCY; PEPTIDES; PRESSURE;
D O I
10.1111/j.1365-2249.2011.04319.x
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
P>Human immunodeficiency virus (HIV)-1 protease is a known target of CD8+ T cell responses, but it is the only HIV-1 protein in which no fully characterized HIV-1 protease CD4 epitopes have been identified to date. We investigated the recognition of HIV-1 protease by CD4+ T cells from 75 HIV-1-infected, protease inhibitor (PI)-treated patients, using the 5,6-carboxyfluorescein diacetate succinimidyl ester-based proliferation assay. In order to identify putative promiscuous CD4+ T cell epitopes, we used the TEPITOPE algorithm to scan the sequence of the HXB2 HIV-1 protease. Protease regions 4-23, 45-64 and 73-95 were identified; 32 sequence variants of the mentioned regions, encoding frequent PI-induced mutations and polymorphisms, were also tested. On average, each peptide bound to five of 15 tested common human leucocyte antigen D-related (HLA-DR) molecules. More than 80% of the patients displayed CD4+ as well as CD8+ T cell recognition of at least one of the protease peptides. All 35 peptides were recognized. The response was not associated with particular HLA-DR or -DQ alleles. Our results thus indicate that protease is a frequent target of CD4+ along with CD8+ proliferative T cell responses by the majority of HIV-1-infected patients under PI therapy. The frequent finding of matching CD4+ and CD8+ T cell responses to the same peptides may indicate that CD4+ T cells provide cognate T cell help for the maintenance of long-living protease-specific functional CD8+ T cells.
引用
收藏
页码:90 / 99
页数:10
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