PMID- 19287301
OWN - NLM
STAT- MEDLINE
DCOM- 20090706
LR  - 20211020
IS  - 1473-5571 (Electronic)
IS  - 0269-9370 (Print)
IS  - 0269-9370 (Linking)
VI  - 23
IP  - 7
DP  - 2009 Apr 27
TI  - Multiple T-cell epitopes overlap positively-selected residues in the p1 spacer 
      protein of HIV-1 gag.
PG  - 771-7
LID - 10.1097/QAD.0b013e32832995e0 [doi]
AB  - OBJECTIVES: The p1 region of HIV-1 gag contains the frameshift stem-loop, gag-pol 
      transframe and a protease cleavage site that are crucial for viral assembly, 
      replication and infectivity. Identifying and characterizing CD8+ epitopes that 
      are under host immune selection in this region will help in designing effective 
      vaccines for HIV-1. DESIGN: An approach combining bioinformatical analysis and 
      interferon gamma enzyme-linked immunosorbent spot (ELISPOT) assays is used to 
      identify and characterize the epitopes. Potential human leukocyte antigen 
      (HLA)-restricted epitopes were identified by correlating the positively-selected 
      mutations with host HLA alleles. METHODS: ELISPOT analysis with overlapping 
      peptides was used to confirm and characterize the epitopes. RESULTS: Four 
      positively-selected residues were significantly associated with HLA class I 
      alleles, including HLA B*1302 (K4R, P = 0.0008 and I5L, P = 0.0108), A*7401 (S9N, 
      P = 0.0002) and A*30 genotypes (P7S, P = 0.009), suggesting epitopes restricted 
      by these alleles are present in this region. ELISPOT analysis with patient 
      peripheral blood mononuclear cells (PBMCs) identified seven novel epitopes 
      restricted by the 3 alleles. Two types of epitopes were observed in this region 
      based on the ELISPOT responses, Type I: the positively-selected variation does 
      not affect CD8+ T-cell responses; and Type II: the CD8+ T-cell responses are 
      determined by the epitope variants. CONCLUSION: We identified and characterized 
      seven novel CD8+ epitopes in the p1 spacer protein region. Classifying the 
      effects of positively-selected variants on CD8+ T-cell responses will help in 
      designing effective vaccines for HIV-1.
FAU - Semeniuk, Christina A
AU  - Semeniuk CA
AD  - Department of Medical Microbiology, University of Manitoba, National Microbiology 
      Laboratory, 1015 Arlington Street, Winnipeg, Manitoba R3E 3R2, Canada. 
      ma_luo@phac-aspc.gc.ca
FAU - McKinnon, Lyle
AU  - McKinnon L
FAU - Peters, Harold O
AU  - Peters HO
FAU - Gubbins, Michael
AU  - Gubbins M
FAU - Mao, Xiaojuan
AU  - Mao X
FAU - Ball, Terry B
AU  - Ball TB
FAU - Luo, Ma
AU  - Luo M
FAU - Plummer, Francis A
AU  - Plummer FA
LA  - eng
GR  - R01 AI048373-01/AI/NIAID NIH HHS/United States
GR  - R01 AI056980-05/AI/NIAID NIH HHS/United States
GR  - R01 AI056980-04/AI/NIAID NIH HHS/United States
GR  - R01 AI056980-02/AI/NIAID NIH HHS/United States
GR  - R01 AI048373-03/AI/NIAID NIH HHS/United States
GR  - R01 AI056980-03/AI/NIAID NIH HHS/United States
GR  - R01 AI056980-01A1/AI/NIAID NIH HHS/United States
GR  - R01 AI048373-02/AI/NIAID NIH HHS/United States
GR  - R01 A149383/PHS HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - AIDS
JT  - AIDS (London, England)
JID - 8710219
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (Gene Products, gag)
RN  - 0 (HLA Antigens)
RN  - 0 (Peptides)
RN  - 0 (RNA, Viral)
SB  - IM
MH  - Alleles
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Cells, Cultured
MH  - Epitopes, T-Lymphocyte/genetics/*immunology
MH  - Female
MH  - Gene Products, gag/genetics/*immunology
MH  - HIV Infections/genetics/*immunology
MH  - HIV-1/*immunology
MH  - HLA Antigens/genetics/immunology
MH  - Humans
MH  - Immunohistochemistry
MH  - Peptides/genetics/immunology
MH  - RNA, Viral/genetics/immunology
PMC - PMC2734095
MID - NIHMS99315
COIS- There are no conflicts of interest.
EDAT- 2009/03/17 09:00
MHDA- 2009/07/07 09:00
PMCR- 2010/04/27
CRDT- 2009/03/17 09:00
PHST- 2009/03/17 09:00 [entrez]
PHST- 2009/03/17 09:00 [pubmed]
PHST- 2009/07/07 09:00 [medline]
PHST- 2010/04/27 00:00 [pmc-release]
AID - 10.1097/QAD.0b013e32832995e0 [doi]
PST - ppublish
SO  - AIDS. 2009 Apr 27;23(7):771-7. doi: 10.1097/QAD.0b013e32832995e0.