Important contribution of p15 Gag-specific responses to the total Gag-specific CTL responses.
OBJECTIVE
HIV-1 p15 Gag and its protease cleavage products, NCp7 and p6, are believed to play a major role in viral infectivity and assembly during the early and late stages of the retroviral life cycle. However, the extent to which p15 Gag is targeted by the host immune system in natural infection as well as precise cytotoxic T lymphocyte (CTL) epitopes within this protein remains to be defined.


METHODS
In this study, 57 HIV-1 infected individuals and 10 HIV-1 negative controls were screened for CD8 and CD4 T-cell responses using overlapping peptides spanning the entire p15 Gag protein as well as the p17 Gag and p24 Gag proteins. Peptide-specific interferon-gamma production was measured by Elispot assay and flow-based intracellular cytokine quantification, and cytotoxic activity was confirmed after isolation of peptide-specific CD8 T-cell lines.


RESULTS
CD8 T lymphocytes specific to p15 Gag were found in 46% (26/57) of HIV-1 infected individuals studied and contributed on average 17% (range, 0-100%) to the total Gag-specific T-cell responses. Responses were clustered within three immunodominant regions of p15 Gag, mapping to important functional sites. These studies also include the description of the first three optimally defined CTL epitopes within p15 Gag.


CONCLUSIONS
These results indicate that p15 Gag is frequently recognized by HIV-1-specific CD8 T cells in HIV-1 infection and will be important in the comprehensive assessments of CTL responses in infected persons, as well as the design and testing of future HIV-1 vaccines and immunotherapeutic interventions.
Yu
Xu G
XG
Partners AIDS Research Center, Infectious Disease Division, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Shang
Hong
H
Addo
Marylyn M
MM
Eldridge
Robert L
RL
Phillips
Mary N
MN
Feeney
Margaret E
ME
Strick
Daryld
D
Brander
Christian
C
Goulder
Philip J R
PJ
Rosenberg
Eric S
ES
Walker
Bruce D
BD
Altfeld
Marcus
M
D000595:Amino Acid Sequence; D016022:Case-Control Studies; D002460:Cell Line; D018604:Epitope Mapping; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology*; D015488:HIV Antigens / Q000235:genetics; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D015234:HLA-A Antigens; D015789:HLA-A2 Antigen; D006801:Humans; D066298:In Vitro Techniques; D019590:Nucleocapsid Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D054301:gag Gene Products, Human Immunodeficiency Virus
D015683:Gene Products, gag; D015488:HIV Antigens; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D019590:Nucleocapsid Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; C060295:p15 gag protein, Human immunodeficiency virus 1