Epitope mapping of HIV-specific CD8+ T cells in a cohort dominated by clade A1 infection.
BACKGROUND
CD8+ T cell responses are often detected at large magnitudes in HIV-infected subjects, and eliciting these responses is the central aim of many HIV-1 vaccine strategies. Population differences in CD8+ T cell epitope specificity will need to be understood if vaccines are to be effective in multiple geographic regions.


RESULTS
In a large Kenyan cohort, we compared responsive CD8+ T cell HIV-1 Env overlapping peptides (OLPs) to Best Defined Epitopes (BDEs), many of which have been defined in clade B infection. While the majority of BDEs (69%) were recognized in this population, nearly half of responsive OLPs (47%) did not contain described epitopes. Recognition frequencies of BDEs were inversely correlated to epitopic sequence differences between clade A1 and BDE (P = 0.019), and positively selected residues were more frequent in "new" OLPs (without BDEs). We assessed the impact of HLA and TAP binding on epitope recognition frequencies, focusing on predicted and actual epitopes in the HLA B7 supertype.


CONCLUSIONS
Although many previously described CD8 epitopes were recognized, several novel CD8 epitopes were defined in this population, implying that epitope mapping efforts have not been completely exhausted. Expansion of these studies will be critical to understand population differences in CD8 epitope recognition.
McKinnon
Lyle R
LR
Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada. sijuisijali@gmail.com
Mao
Xiaojuan
X
Kimani
Joshua
J
Wachihi
Charles
C
Semeniuk
Christina
C
Mendoza
Mark
M
Liang
Binhua
B
Luo
Ma
M
Fowke
Keith R
KR
Plummer
Francis A
FA
Ball
T Blake
TB
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D015331:Cohort Studies; D018450:Disease Progression; D018604:Epitope Mapping / Q000379:methods*; D000939:Epitopes / Q000737:chemistry; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D005843:Geography; D006678:HIV / Q000378:metabolism*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D006680:HLA Antigens / Q000737:chemistry; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007630:Kenya
D000939:Epitopes; D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens; D007371:Interferon-gamma