Human Leukocyte Antigen F Presents Peptides and Regulates Immunity through Interactions with NK Cell Receptors.
Immunity
; 46(6): 1018-1029.e7, 2017 06 20.
Article
in En
| MEDLINE
| ID: mdl-28636952
ABSTRACT
Evidence is mounting that the major histocompatibility complex (MHC) molecule HLA-F (human leukocyte antigen F) regulates the immune system in pregnancy, infection, and autoimmunity by signaling through NK cell receptors (NKRs). We present structural, biochemical, and evolutionary analyses demonstrating that HLA-F presents peptides of unconventional length dictated by a newly arisen mutation (R62W) that has produced an open-ended groove accommodating particularly long peptides. Compared to empty HLA-F open conformers (OCs), HLA-F tetramers bound with human-derived peptides differentially stained leukocytes, suggesting peptide-dependent engagement. Our in vitro studies confirm that NKRs differentiate between peptide-bound and peptide-free HLA-F. The complex structure of peptide-loaded ß2m-HLA-F bound to the inhibitory LIR1 revealed similarities to high-affinity recognition of the viral MHC-I mimic UL18 and a docking strategy that relies on contacts with HLA-F as well as ß2m, thus precluding binding to HLA-F OCs. These findings provide a biochemical framework to understand how HLA-F could regulate immunity via interactions with NKRs.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Viral Proteins
/
Killer Cells, Natural
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Histocompatibility Antigens Class I
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Molecular Mimicry
/
Receptors, Natural Killer Cell
Limits:
Female
/
Humans
/
Pregnancy
Language:
En
Journal:
Immunity
Journal subject:
ALERGIA E IMUNOLOGIA
Year:
2017
Type:
Article
Affiliation country:
United States