Group M consensus Gag and Nef peptides are as efficient at detecting clade A1 and D cross-subtype T-cell functions as subtype-specific consensus peptides.
OBJECTIVE
Evaluating HIV-1 specific T-cell response in African populations is sometimes compromised by extensive virus diversity and paucity of non-clade B reagents. We evaluated whether consensus group M (ConM) peptides could serve as comparable substitutes for detecting immune responses in clade A and clade D HIV-1 infection.


METHODS
Frequencies, breadths and polyfunctionality (≥ 3 functions: IFN-γ, IL-2, TNF-α and Perforin) of HIV-specific responses utilizing ConM, ConA and ConD Gag and Nef peptides was compared.


RESULTS
Median genetic distances of infecting gag sequences from consensus group M were (8.9%, IQR 8.2-9.7 and 9%, IQR 3.3-10) for consensus A and D, respectively. Of 24 subjects infected with A and D clade virus, Gag responses were detected in comparable proportions of subjects when using ConM peptides 22/24, ConA peptides 17/24, and ConD peptides 21/24; p=0.12. Nef responses were also detected at similar proportions of subjects when using ConM peptides 15/23, ConA peptides 19/23, and ConD peptides 16/23, p=0.39. Virus-specific CD4+ and CD8+ T-cell polyfunctionality were also detected in similar proportions of infected individuals when using different peptide sets.


CONCLUSIONS
These data support the use of consensus group M overlapping peptide sets as reagents for detecting HIV-specific responses in a clade A and D infected population, but underscore the limitations of utilizing these reagents when evaluating the breadth of virus-specific responses.
MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda.
S
S
Mugaba
MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda.
R
R
Nakiboneka
MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda.
M
M
Nanyonjo
MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda.
D
D
Bugembe-Lule
MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda.
I
I
Kaddu
MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda.
B
B
Nanteza
MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda.
R
R
Tweyongyere
MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda; London School of Hygiene and Tropical Medicine, United Kingdom.
P
P
Kaleebu
MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda. Electronic address: jennifer.serwanga@mrcuganda.org.
J
J
Serwanga
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016384:Consensus Sequence; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000145:classification* / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000276:immunology; D054353:Perforin / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics*; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000235:genetics*
D007376:Interleukin-2; D010455:Peptides; D014409:Tumor Necrosis Factor-alpha; D054301:gag Gene Products, Human Immunodeficiency Virus; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1; D054353:Perforin; D007371:Interferon-gamma
Group M peptides; HIV-1 diversity; T-cell responses