title: Profile of T cell recognition of HIV type 1 consensus group M Gag and Nef peptides in a clade A1- and D-infected Ugandan population.
abstract: Reagents for evaluating non-clade B HIV-specific T cell responses are uncommon. Peptides based on highly conserved HIV-1 consensus group M sequences that are phylogenetically closer to most circulating strains may provide potential alternative reagents in populations with diverse infections, and may be relevant for vaccine design. Recognition of such reagents in clade A1-and D-infected populations has not been previously evaluated. Interferon (IFN)-γ ELISpot assay was used to evaluate T cell recognition of Gag and Nef peptides based on consensus group M sequences in 50 treatment-naive adults predominantly infected with HIV-1 clades A1 and D. Gag-induced T cell responses were correlated with gag sequence diversity. Infecting clades were determined from gag sequences for 45 of the 50 subjects as 40% clade A1 (18/45), 45% clade D (20/45), 2% clade C (1/45), 2% A1/C recombinant (1/45), 2% A1/D (1/45), 7% CRF10_CD (3/45), and 2% U (unclassifiable) (1/45). The mean genetic divergence and diversity of clade A and D gag region compared to group M consensus sequences at synonymous and nonsynonymous nucleotide and amino acid levels were not always significant. Gag peptides were targeted at significantly higher frequency [88% (44/50)] than Nef [64% (32/50)]; p=0.014, although their mean IFN-γ magnitudes were comparable ([3703 (95% CI 2567-4839)] vs. [2120 (95% CI 478-3762)]), respectively. Measurable virus-induced IFN-γ responses were detected in 96% (48/50) individuals, primarily targeting the more conserved Gag p24 and Nef central core regions. Use of these reagents to screen for HIV-specific IFN-γ responses may mitigate the challenge of viral diversity; although this targeting is apparently biased toward a few highly conserved epitopes.
authors.affiliation: MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda. jennifer.serwanga@mrcuganda.org
authors.forename: Jennifer
authors.initials: J
authors.lastname: Serwanga
authors.forename: Susan
authors.initials: S
authors.lastname: Mugaba
authors.forename: Edward
authors.initials: E
authors.lastname: Pimego
authors.forename: Bridget
authors.initials: B
authors.lastname: Nanteza
authors.forename: Fred
authors.initials: F
authors.lastname: Lyagoba
authors.forename: Susan
authors.initials: S
authors.lastname: Nakubulwa
authors.forename: Laura
authors.initials: L
authors.lastname: Heath
authors.forename: Rebecca N
authors.initials: RN
authors.lastname: Nsubuga
authors.forename: Nicaise
authors.initials: N
authors.lastname: Ndembi
authors.forename: Frances
authors.initials: F
authors.lastname: Gotch
authors.forename: Pontiano
authors.initials: P
authors.lastname: Kaleebu
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000328:Adult; D044383:Black People; D005260:Female; D006679:HIV Seropositivity / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D008297:Male; D017471:Receptors, Interferon / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014454:Uganda; D019562:Viral Load / Q000276:immunology; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology*; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000276:immunology*; D000096743:Interferon gamma Receptor
chemical_list: D016915:AIDS Vaccines; D016056:Immunodominant Epitopes; D007371:Interferon-gamma; D017471:Receptors, Interferon; D054301:gag Gene Products, Human Immunodeficiency Virus; D054311:nef Gene Products, Human Immunodeficiency Virus; D000096743:Interferon gamma Receptor