PMID- 33126487
OWN - NLM
STAT- MEDLINE
DCOM- 20210329
LR  - 20210329
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 21
IP  - 21
DP  - 2020 Oct 28
TI  - The Loss of HLA-F/KIR3DS1 Ligation Is Mediated by Hemoglobin Peptides.
LID - 10.3390/ijms21218012 [doi]
LID - 8012
AB  - The human leukocyte antigen (HLA)-Ib molecule, HLA-F, is known as a CD4(+) T-cell 
      protein and mediator of HIV progression. While HLA-Ia molecules do not have the 
      chance to select and present viral peptides for immune recognition due to protein 
      downregulation, HLA-F is upregulated. Post HIV infection, HLA-F loses the 
      affinity to its activating receptor KIR3DS1 on NK cells leading to progression of 
      the HIV infection. Several studies aimed to solve the question of the biophysical 
      interface between HLA ligands and their cognate receptors. It became clear that 
      even an invariant HLA molecule can be structurally modified by the variability of 
      the bound peptide. We recently discovered the ability of HLA-F to select and 
      present peptides and the HLA-F allele-specific peptide selection from the 
      proteomic content using soluble HLA (sHLA) technology and a sophisticated MS 
      method. We established recombinant K562 cells that express membrane-bound 
      HLA-F*01:01, 01:03 or 01:04 complexes. While a recombinant soluble form of 
      KIR3DS1 did not bind to the peptide-HLA-F complexes, acid elution of the peptides 
      resulted in the presentation of HLA-F open conformers, and the binding of the 
      soluble KIR3DS1 receptor increased. We used CD4(+)/HIV(-) and CD4(+)/HIV(+) cells 
      and performed an MS proteome analysis. We could detect hemoglobin as 
      significantly upregulated in CD4(+) T-cells post HIV infection. The expression of 
      cellular hemoglobin in nonerythroid cells has been described, yet HLA-Ib 
      presentation of hemoglobin-derived peptides is novel. Peptide sequence analysis 
      from HLA-F allelic variants featured hemoglobin peptides as dominant and shared. 
      The reciprocal experiment of binding hemoglobin peptide fractions to the HLA-F 
      open conformers resulted in significantly diminished receptor recognition. These 
      results underpin the molecular involvement of HLA-F and its designated peptide 
      ligand in HIV immune escape.
FAU - Ho, Gia-Gia T
AU  - Ho GT
AD  - Institute for Transfusion Medicine, Hannover Medical School, Carl-Neuberg-Str. 1, 
      30625 Hannover, Germany.
FAU - Hiemisch, Wiebke
AU  - Hiemisch W
AD  - Institute for Transfusion Medicine, Hannover Medical School, Carl-Neuberg-Str. 1, 
      30625 Hannover, Germany.
FAU - Pich, Andreas
AU  - Pich A
AD  - Institute of Toxicology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 
      Hannover, Germany.
FAU - Behrens, Georg M N
AU  - Behrens GMN
AUID- ORCID: 0000-0003-3111-621X
AD  - Department of Rheumatology and Immunology, Hannover Medical School, 
      Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
AD  - German Center for Infections Research, partner site Hannover-Braunschweig, 
      Inhoffenstrasse 7, 38124 Braunschweig, Germany.
FAU - Blasczyk, Rainer
AU  - Blasczyk R
AUID- ORCID: 0000-0003-3875-3190
AD  - Institute for Transfusion Medicine, Hannover Medical School, Carl-Neuberg-Str. 1, 
      30625 Hannover, Germany.
FAU - Bade-Doeding, Christina
AU  - Bade-Doeding C
AUID- ORCID: 0000-0002-5826-1989
AD  - Institute for Transfusion Medicine, Hannover Medical School, Carl-Neuberg-Str. 1, 
      30625 Hannover, Germany.
LA  - eng
GR  - MED1912/Hector foundation/
PT  - Journal Article
DEP - 20201028
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (HLA-F antigens)
RN  - 0 (Hemoglobins)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (KIR3DS1 protein, human)
RN  - 0 (Peptide Fragments)
RN  - 0 (Proteome)
RN  - 0 (Receptors, KIR3DS1)
SB  - IM
MH  - CD4-Positive T-Lymphocytes/*immunology
MH  - HIV Infections/*immunology/metabolism/virology
MH  - HIV-1/immunology
MH  - Hemoglobins/*metabolism
MH  - Histocompatibility Antigens Class I/*immunology/metabolism
MH  - Humans
MH  - Peptide Fragments/*metabolism
MH  - Protein Binding
MH  - Proteome/*analysis
MH  - Receptors, KIR3DS1/*immunology/metabolism
PMC - PMC7672607
OTO - NOTNLM
OT  - HLA-F
OT  - KIR3DS1
OT  - peptides
OT  - proteome
COIS- The authors declare no conflict of interest.
EDAT- 2020/11/01 06:00
MHDA- 2021/03/30 06:00
PMCR- 2020/11/01
CRDT- 2020/10/31 01:01
PHST- 2020/08/25 00:00 [received]
PHST- 2020/10/16 00:00 [revised]
PHST- 2020/10/21 00:00 [accepted]
PHST- 2020/10/31 01:01 [entrez]
PHST- 2020/11/01 06:00 [pubmed]
PHST- 2021/03/30 06:00 [medline]
PHST- 2020/11/01 00:00 [pmc-release]
AID - ijms21218012 [pii]
AID - ijms-21-08012 [pii]
AID - 10.3390/ijms21218012 [doi]
PST - epublish
SO  - Int J Mol Sci. 2020 Oct 28;21(21):8012. doi: 10.3390/ijms21218012.