PMID- 24384691
OWN - NLM
STAT- MEDLINE
DCOM- 20140917
LR  - 20211021
IS  - 1473-5571 (Electronic)
IS  - 0269-9370 (Linking)
VI  - 28
IP  - 4
DP  - 2014 Feb 20
TI  - The link between CD8(+) T-cell antigen-sensitivity and HIV-suppressive capacity 
      depends on HLA restriction, target epitope and viral isolate.
PG  - 477-86
LID - 10.1097/QAD.0000000000000175 [doi]
AB  - BACKGROUND: Although it is established that CD8 T-cell immunity is critical for 
      the control of HIV replication in vivo, the key factors that determine antiviral 
      efficacy are yet to be fully elucidated. Antigen-sensitivity and T-cell receptor 
      (TCR) avidity have been identified as potential determinants of CD8(+) T-cell 
      efficacy. However, there is no general consensus in this regard because the 
      relationship between these parameters and the control of HIV infection has been 
      established primarily in the context of immunodominant CD8(+) T-cell responses 
      against the Gag(2)(6)(3)(-)(2)(7)(2) KK10 epitope restricted by human leukocyte antigen 
      (HLA)-B27. METHODS: To investigate the relationship between antigen-sensitivity, 
      TCR avidity and HIV-suppressive capacity in vitro across epitope specificities 
      and HLA class I restriction elements, we used a variety of techniques to study 
      CD8(+) T-cell clones specific for Nef(7)(3)(-)(8)(2) QK10 and Gag(2)(0)(-)(2)(9) RY10, both restricted 
      by HLA-A3, alongside CD8(+) T-cell clones specific for Gag(2)(6)(3)(-)(2)(7)(2) KK10. RESULTS: 
      For each targeted epitope, the linked parameters of antigen-sensitivity and TCR 
      avidity correlated directly with antiviral efficacy. However, marked differences 
      in HIV-suppressive capacity were observed between epitope specificities, HLA 
      class I restriction elements and viral isolates. CONCLUSIONS: Collectively, these 
      data emphasize the central role of the TCR as a determinant of CD8(+) T-cell 
      efficacy and demonstrate that the complexities of antigen recognition across 
      epitope and HLA class I boundaries can confound simple relationships between TCR 
      engagement and HIV suppression.
FAU - Lissina, Anna
AU  - Lissina A
AD  - aINSERM UMR S 945, Infections and Immunity, Universite Pierre et Marie 
      Curie-Paris6, Hopital Pitie-Salpetriere, Paris, France bInstitute of Infection 
      and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, Wales, 
      UK cInstitut Pasteur, Unite de Regulation des Infections Retrovirales, Paris, 
      France. *Anna Lissina and Solene Fastenackels contributed equally to this writing 
      of this work. daggerCurrent address: Centro de Investigacion en Enfermedades 
      Infecciosas, Instituto Nacional de Enfermedades Respiratorias, Mexico City, 
      Mexico.
FAU - Fastenackels, Solene
AU  - Fastenackels S
FAU - Inglesias, Maria C
AU  - Inglesias MC
FAU - Ladell, Kristin
AU  - Ladell K
FAU - McLaren, James E
AU  - McLaren JE
FAU - Briceno, Olivia
AU  - Briceno O
FAU - Gostick, Emma
AU  - Gostick E
FAU - Papagno, Laura
AU  - Papagno L
FAU - Autran, Brigitte
AU  - Autran B
FAU - Sauce, Delphine
AU  - Sauce D
FAU - Price, David A
AU  - Price DA
FAU - Saez-Cirion, Asier
AU  - Saez-Cirion A
FAU - Appay, Victor
AU  - Appay V
LA  - eng
GR  - 100326/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - AIDS
JT  - AIDS (London, England)
JID - 8710219
RN  - 0 (Epitopes)
RN  - 0 (HIV Antigens)
RN  - 0 (HLA Antigens)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (gag Gene Products, Human Immunodeficiency Virus)
RN  - 0 (nef Gene Products, Human Immunodeficiency Virus)
SB  - IM
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Epitopes/*immunology
MH  - HIV Antigens/*immunology
MH  - HIV Infections/*immunology/*virology
MH  - HLA Antigens/*immunology
MH  - Humans
MH  - Receptors, Antigen, T-Cell/*immunology
MH  - gag Gene Products, Human Immunodeficiency Virus/immunology
MH  - nef Gene Products, Human Immunodeficiency Virus/immunology
EDAT- 2014/01/05 06:00
MHDA- 2014/09/18 06:00
CRDT- 2014/01/04 06:00
PHST- 2014/01/04 06:00 [entrez]
PHST- 2014/01/05 06:00 [pubmed]
PHST- 2014/09/18 06:00 [medline]
AID - 10.1097/QAD.0000000000000175 [doi]
PST - ppublish
SO  - AIDS. 2014 Feb 20;28(4):477-86. doi: 10.1097/QAD.0000000000000175.