Differential immunogenicity of HIV-1 clade C proteins in eliciting CD8+ and CD4+ cell responses.
BACKGROUND
The relative immunogenicity of human immunodeficiency virus type 1 (HIV-1) proteins for CD8+ and CD4+ cell responses has not been defined.


METHODS
HIV-1-specific T cell responses were evaluated in 65 chronically HIV-1-infected untreated subjects by interferon- gamma flow cytometry with peptides spanning the clade C consensus sequence.


RESULTS
The magnitude of HIV-1-specific CD8+ T cell responses correlated significantly with CD4+ cell responses, but the percentage of CD8+ T cells directed against HIV-1 (median, 2.76%) was always greater than that of CD4+ cells (median, 0.24%). Although CD8+ T cell responses were equally distributed among Gag, Pol, and the regulatory and accessory proteins, Gag was the dominant target for CD4+ cell responses. There was no consistent relationship between virus-specific CD8+ or CD4+ cell response and viral load. However, the median viral load in subjects in whom Gag was the dominant CD8+ T cell target was significantly lower than that in subjects in whom non-Gag proteins were the main target (P=.007).


CONCLUSIONS
Gag-specific responses dominate the CD4+ T cell response to HIV, whereas CD8+ T cell responses are broadly distributed, which indicates differential immunogenicity of these cells against HIV-1. The preferential targeting of Gag by CD8+ T cells is associated with enhanced control of viral load.
Ramduth
Danni
D
HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa. ramduthd1@ukzn.ac.za
Chetty
Polan
P
Mngquandaniso
Nolwandle Cyloria
NC
Nene
Nonhlanhla
N
Harlow
Jason Davis
JD
Honeyborne
Isobella
I
Ntumba
Nelisiwe
N
Gappoo
Sharika
S
Henry
Chiara
C
Jeena
Prakash
P
Addo
Marylyn Martina
MM
Altfeld
Marcus
M
Brander
Christian
C
Day
Cheryl
C
Coovadia
Hoosen
H
Kiepiela
Photini
P
Goulder
Philip
P
Walker
Bruce
B
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002908:Chronic Disease; D005260:Female; D015683:Gene Products, gag / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000145:classification / Q000276:immunology*; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D020543:Proteome / Q000276:immunology; D019562:Viral Load; D014764:Viral Proteins / Q000276:immunology*
D015683:Gene Products, gag; D020543:Proteome; D014764:Viral Proteins