title: The immune response to the RT181-189 epitope in HIV-1-infected patients is associated with viral sequence polymorphism flanking the epitope.
abstract: 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-γ 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.
authors.affiliation: EA4271 Laboratoire d'Immunovirologie et Polymorphisme Génétique, Université de Nantes, Nantes, France.
authors.forename: Yovana
authors.initials: Y
authors.lastname: Pacheco
authors.forename: Clotilde
authors.initials: C
authors.lastname: Allavena
authors.forename: Yannick
authors.initials: Y
authors.lastname: Guilloux
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Mueller-Schmucker
authors.forename: Angela G
authors.initials: AG
authors.lastname: Hueckelhoven
authors.forename: Elisabeth
authors.initials: E
authors.lastname: André-Garnier
authors.forename: François
authors.initials: F
authors.lastname: Cleon
authors.forename: Virginie
authors.initials: V
authors.lastname: Ferré
authors.forename: Audrey
authors.initials: A
authors.lastname: Rodallec
authors.forename: Eric
authors.initials: E
authors.lastname: Billaud
authors.forename: Thomas
authors.initials: T
authors.lastname: Harrer
authors.forename: François
authors.initials: F
authors.lastname: Raffi
authors.forename: Dorian
authors.initials: D
authors.lastname: McIlroy
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000276:immunology; D002478:Cells, Cultured; D024882:Drug Resistance, Viral / Q000235:genetics*; D058501:Enzyme-Linked Immunospot Assay; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D015658:HIV Infections / Q000235:genetics* / Q000473:pathology; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology; D015789:HLA-A2 Antigen / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D013602:T-Lymphocytes, Cytotoxic / Q000821:virology
chemical_list: D019380:Anti-HIV Agents; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D007371:Interferon-gamma; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase