PMID- 23952339
OWN - NLM
STAT- MEDLINE
DCOM- 20140108
LR  - 20231213
IS  - 1365-2249 (Electronic)
IS  - 0009-9104 (Print)
IS  - 0009-9104 (Linking)
VI  - 174
IP  - 3
DP  - 2013 Dec
TI  - Dimorphic HLA-B signal peptides differentially influence HLA-E- and natural 
      killer cell-mediated cytolysis of HIV-1-infected target cells.
PG  - 414-23
LID - 10.1111/cei.12187 [doi]
AB  - As a mechanism of self-protection, signal peptides cleaved from human leukocyte 
      antigen (HLA) class I products bind to HLA-E before the complex interacts with 
      the natural killer (NK) cell receptor CD94/NKG2A to inhibit NK-mediated cell 
      lysis. Two types of the signal peptides differ in their position 2 (P2) anchor 
      residue, with P2-methionine (P2-M) having higher HLA-E binding affinity than 
      P2-threonine (P2-T). All HLA-A and HLA-C molecules carry P2-M, whereas HLA-B 
      products have either P2-M or P2-T. Epidemiological evidence suggests that P2-M is 
      unfavourable in the context of HIV-1 infection, being associated with accelerated 
      acquisition of HIV-1 infection in two African cohorts. To begin elucidating the 
      functional mechanism, we studied NK-mediated killing of CD4(+) T cells and 
      monocyte-derived macrophages infected with two laboratory-adapted HIV-1 strains 
      and two transmitted/founder (T/F) viruses. In the presence of target cells 
      derived from individuals with the three HLA-B P2 genotypes (M/M, M/T and T/T), 
      NK-mediated cytolysis was elevated consistently for P2-T in a dose-dependent 
      manner for all cell and virus combinations tested (P = 0.008-0.03). Treatment of 
      target cells with an anti-HLA-E monoclonal antibody restored NK-mediated 
      cytolysis of cells expressing P2-M. Observations on cell lysis were also 
      substantiated by measurements of HIV-1 p24 antigen in the culture supernatants. 
      Overall, our experiments indicate that the anti-HIV-1 function mediated by NK 
      cells is compromised by P2-M, corroborating the association of HLA-B genotype 
      encoding P2-M with accelerated HIV-1 acquisition.
CI  - (c) 2013 British Society for Immunology.
FAU - Merino, A M
AU  - Merino AM
AD  - Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA; 
      Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, 
      USA.
FAU - Sabbaj, S
AU  - Sabbaj S
FAU - Easlick, J
AU  - Easlick J
FAU - Goepfert, P
AU  - Goepfert P
FAU - Kaslow, R A
AU  - Kaslow RA
FAU - Tang, J
AU  - Tang J
LA  - eng
GR  - P30 AI027767/AI/NIAID NIH HHS/United States
GR  - R01 AI064060/AI/NIAID NIH HHS/United States
GR  - R01 AI071906/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - England
TA  - Clin Exp Immunol
JT  - Clinical and experimental immunology
JID - 0057202
RN  - 0 (HIV Core Protein p24)
RN  - 0 (HLA-B Antigens)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (NK Cell Lectin-Like Receptor Subfamily C)
RN  - 0 (NK Cell Lectin-Like Receptor Subfamily D)
RN  - 0 (Protein Sorting Signals)
SB  - IM
MH  - CD4-Positive T-Lymphocytes/*immunology
MH  - Cells, Cultured
MH  - HIV Core Protein p24/analysis
MH  - HIV Infections/*immunology
MH  - HIV-1/immunology
MH  - HLA-B Antigens/*immunology/metabolism
MH  - Histocompatibility Antigens Class I/*immunology/metabolism
MH  - Humans
MH  - Killer Cells, Natural/*immunology
MH  - Macrophages/immunology
MH  - NK Cell Lectin-Like Receptor Subfamily C/immunology
MH  - NK Cell Lectin-Like Receptor Subfamily D/immunology
MH  - Protein Sorting Signals
MH  - HLA-E Antigens
PMC - PMC3826307
OTO - NOTNLM
OT  - HIV-1
OT  - HLA-B
OT  - HLA-E
OT  - natural killer cell
OT  - signal peptide
EDAT- 2013/08/21 06:00
MHDA- 2014/01/09 06:00
PMCR- 2014/12/01
CRDT- 2013/08/20 06:00
PHST- 2013/08/11 00:00 [accepted]
PHST- 2013/08/20 06:00 [entrez]
PHST- 2013/08/21 06:00 [pubmed]
PHST- 2014/01/09 06:00 [medline]
PHST- 2014/12/01 00:00 [pmc-release]
AID - 10.1111/cei.12187 [doi]
PST - ppublish
SO  - Clin Exp Immunol. 2013 Dec;174(3):414-23. doi: 10.1111/cei.12187.