PMID- 23740989
OWN - NLM
STAT- MEDLINE
DCOM- 20130918
LR  - 20211021
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 87
IP  - 15
DP  - 2013 Aug
TI  - HIV-1 gag cytotoxic T lymphocyte epitopes vary in presentation kinetics relative 
      to HLA class I downregulation.
PG  - 8726-34
LID - 10.1128/JVI.01040-13 [doi]
AB  - Although CD8(+) cytotoxic T lymphocytes (CTLs) are protective in HIV-1 infection, 
      the factors determining their antiviral efficiency are poorly defined. It is 
      proposed that Gag targeting is superior because of very early Gag epitope 
      presentation, allowing early killing of infected cells before Nef-mediated 
      downregulation of human leukocyte antigen class I (HLA-I). To study Gag epitope 
      presentation kinetics, three epitopes (SL977-85, KF11162-172, and TW10240-249) 
      were genetically translocated from their endogenous location in the Rev-dependent 
      (late) gag gene into the Rev-independent (early) nef gene with concomitant 
      mutation of the corresponding endogenous epitopes to nonrecognized sequences. 
      These viruses were compared to the index virus for CTL-mediated suppression of 
      replication and the susceptibility of this antiviral activity to Nef-mediated 
      HLA-I downregulation. SL9-specific CTLs gained activity after SL9 translocation 
      to Nef, going from Nef sensitive to Nef insensitive, indicating that 
      translocation accelerated infected cell recognition from after to before HLA-I 
      downregulation. KF11-specific CTL antiviral activity was unchanged and 
      insensitive to HLA-I downregulation before and after KF11 translocation, 
      suggesting that already rapid recognition of infected cells was not accelerated. 
      However, TW10-specific CTLs that were insensitive to Nef at the baseline became 
      sensitive with reduced antiviral activity after translocation, indicating that 
      translocation retarded epitope expression. Cytosolic peptide processing assays 
      suggested that TW10 was inefficiently generated after translocation to Nef, 
      compared to SL9 and KF11. As a whole, these data demonstrate that epitope 
      presentation kinetics play an important role in CTL antiviral efficiency, that 
      Gag epitopes are not uniformly presented early, and that the epitope context can 
      play a major role in presentation kinetics.
FAU - Balamurugan, Arumugam
AU  - Balamurugan A
AD  - Division of Infectious Diseases, Department of Medicine, Geffen School of 
      Medicine, University of California-Los Angeles, Los Angeles, California, USA.
FAU - Ali, Ayub
AU  - Ali A
FAU - Boucau, Julie
AU  - Boucau J
FAU - Le Gall, Sylvie
AU  - Le Gall S
FAU - Ng, Hwee L
AU  - Ng HL
FAU - Yang, Otto O
AU  - Yang OO
LA  - eng
GR  - R01 AI043203/AI/NIAID NIH HHS/United States
GR  - R01 AI051970/AI/NIAID NIH HHS/United States
GR  - AI043203/AI/NIAID NIH HHS/United States
GR  - AI051970/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130605
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Recombinant Proteins)
RN  - 0 (gag Gene Products, Human Immunodeficiency Virus)
SB  - IM
MH  - Down-Regulation
MH  - Epitopes, T-Lymphocyte/genetics/*immunology
MH  - HIV-1/genetics/*immunology
MH  - Histocompatibility Antigens Class I/biosynthesis/*immunology
MH  - Humans
MH  - Recombinant Proteins/genetics/immunology
MH  - Recombination, Genetic
MH  - T-Lymphocytes, Cytotoxic/*immunology
MH  - gag Gene Products, Human Immunodeficiency Virus/genetics/*immunology
PMC - PMC3719789
EDAT- 2013/06/07 06:00
MHDA- 2013/09/21 06:00
PMCR- 2014/02/01
CRDT- 2013/06/07 06:00
PHST- 2013/06/07 06:00 [entrez]
PHST- 2013/06/07 06:00 [pubmed]
PHST- 2013/09/21 06:00 [medline]
PHST- 2014/02/01 00:00 [pmc-release]
AID - JVI.01040-13 [pii]
AID - 01040-13 [pii]
AID - 10.1128/JVI.01040-13 [doi]
PST - ppublish
SO  - J Virol. 2013 Aug;87(15):8726-34. doi: 10.1128/JVI.01040-13. Epub 2013 Jun 5.