The Immune Response to the RT181-189 Epitope in HIV-1-Infected Patients is Associated with Viral Sequence Polymorphism Flanking the Epitope

被引:2
作者
Pacheco, Yovana [2 ]
Allavena, Clotilde [2 ,3 ]
Guilloux, Yannick [4 ,7 ]
Mueller-Schmucker, Sandra M. [5 ]
Hueckelhoven, Angela G. [5 ]
Andre-Garnier, Elisabeth [2 ,6 ]
Cleon, Francois [2 ]
Ferre, Virginie [2 ,6 ]
Rodallec, Audrey [6 ]
Billaud, Eric [3 ]
Harrer, Thomas [5 ]
Raffi, Francois [2 ,3 ]
McIlroy, Dorian [1 ,2 ,7 ]
机构
[1] EA4271 Fac Med & Pharm, F-44035 Nantes, France
[2] Univ Nantes, Lab Immunovirol & Polymorphisme Genet EA4271, Nantes, France
[3] Hop Hotel Dieu, Serv Infectiol, Nantes, France
[4] INSERM, UMR 892, Nantes, France
[5] Univ Erlangen Nurnberg, Univ Hosp Erlangen, Dept Internal Med 3, D-91054 Erlangen, Germany
[6] Hop Hotel Dieu, Virol Lab, Nantes, France
[7] Univ Nantes, Fac Sci & Tech, Nantes, France
关键词
Cytotoxic T lymphocytes; T-cell epitope; HIV-1 reverse transcriptase; antiviral drug resistance; IMMUNODEFICIENCY-VIRUS TYPE-1; CYTOTOXIC T-LYMPHOCYTES; ANTIRETROVIRAL THERAPY; REVERSE-TRANSCRIPTASE; CELL RESPONSES; HIV-1; INFECTION; RECOGNITION; GAG; VIREMIA; ESCAPE;
D O I
10.1007/s10875-011-9520-z
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Many drug-resistance mutations in HIV-1 reverse transcriptase fall within cytotoxic T lymphocytes (CTL) epitopes, but studies of the response to these epitopes in patients with virological failure are lacking. We therefore compared IFN-gamma ELISPOT responses to the YV9 epitope (RT181-189) covering the lamivudine resistance mutation, M184V, in HLA-A2(+) antiretroviral treatment (ART)-naive patients (n = 19), to those found in HLA-A2(+) patients with virological failure (n = 15). Ten ART-naive patients had an ELISPOT response to the wild-type epitope that cross-reacted with the mutant epitope. Two patients with virological failure showed a specific response to the 184V mutant epitope. Responses against YV9 were strongly associated (p = 0.005) with the presence of a 177E mutation, and the same tendency was observed in an independent cohort of patients (n = 22). These results indicate that variants in flanking residues may influence CTL responses to conserved subdominant HIV-1 epitopes.
引用
收藏
页码:681 / 689
页数:9
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