In a mixed subtype epidemic, the HIV-1 Gag-specific T-cell response is biased towards the infecting subtype.
OBJECTIVE
Southwest Tanzania is affected by an HIV-1 epidemic consisting of subtypes A, C, and D, and their recombinant forms. This study was designed to assess whether the Gag- and Nef-specific T-cell response is biased towards recognizing the infecting subtype.


METHODS
The infecting subtypes were characterized with a Multi-hybridization assay that discriminates between subtypes A, C and D. The interferon-gamma ELISPOT assay was used to detect the Gag- and Nef-specific T-cell responses in freshly isolated peripheral blood mononuclear cells in 56 seropositive patients. To study the HIV-specific T-cell responses, isolate-based Gag and Nef peptide sets representative of the locally occurring subtypes were used. The results were analysed at the total protein and single peptide level.


RESULTS
In the study population, 35% were infected with a pure C subtype, 24% and 23% with ACD or AC recombinant forms, respectively. The total magnitude (P < 0.01) and breadth (P < 0.01) of the Gag-specific T-cell response detected with the subtype C-Gag peptide set was significantly greater than that detected with either the subtype A-Gag or D-Gag peptide sets. No significant difference was observed in the Nef-specific response. In 85% of responses targeting the most immunodominant Gag epitopes with subtype-specific sequence differences, the best recognized epitope variant corresponded to the infecting subtype.


CONCLUSIONS
The Gag-specific T-cell response had a preference for recognizing peptides related to the infecting subtype.
Geldmacher
Christof
C
Mbeya Medical Research Program, Referral Hospital, Mbeya, Tanzania. cgeldmacher@mmrp.org
Currier
Jeffrey R
JR
Gerhardt
Martina
M
Haule
Antelmo
A
Maboko
Leonard
L
Birx
Deborah
D
Gray
Clive
C
Meyerhans
Andreas
A
Cox
Josephine
J
Hoelscher
Michael
M
D000595:Amino Acid Sequence; D004196:Disease Outbreaks; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D015683:Gene Products, gag / Q000276:immunology; D015693:Gene Products, nef / Q000276:immunology; D015750:Genes, gag / Q000276:immunology*; D015658:HIV Infections / Q000453:epidemiology / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000145:classification* / Q000235:genetics / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D016056:Immunodominant Epitopes / Q000276:immunology; D008969:Molecular Sequence Data; D017354:Point Mutation; D011446:Prospective Studies; D013601:T-Lymphocytes / Q000276:immunology; D013636:Tanzania / Q000453:epidemiology; D054311:nef Gene Products, Human Immunodeficiency Virus
D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag; D015693:Gene Products, nef; D016056:Immunodominant Epitopes; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1