UNIGE document Scientific Article
previous document  unige:111074  next document
add to browser collection

LILRB1 polymorphisms influence posttransplant HCMV susceptibility and ligand interactions

Yu, Kang
Davidson, Chelsea L
Wójtowicz, Agnieszka
Lisboa, Luiz
Wang, Ting
Airo, Adriana M
Buratto, Jeremie
show hidden authors show all authors [1 - 18]
Published in Journal of Clinical Investigation. 2018, vol. 128, no. 4, p. 1523-1537
Abstract UL18 is a human CMV (HCMV) MHC class I (MHCI) homolog that efficiently inhibits leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1)+ NK cells. We found an association of LILRB1 polymorphisms in the regulatory regions and ligand-binding domains with control of HCMV in transplant patients. Naturally occurring LILRB1 variants expressed in model NK cells showed functional differences with UL18 and classical MHCI, but not with HLA-G. The altered functional recognition was recapitulated in binding assays with the binding domains of LILRB1. Each of 4 nonsynonymous substitutions in the first 2 LILRB1 immunoglobulin domains contributed to binding with UL18, classical MHCI, and HLA-G. One of the polymorphisms controlled addition of an N-linked glycan, and that mutation of the glycosylation site altered binding to all ligands tested, including enhancing binding to UL18. Together, these findings indicate that specific LILRB1 alleles that allow for superior immune evasion by HCMV are restricted by mutations that limit LILRB1 expression selectively on NK cells. The polymorphisms also maintained an appropriate interaction with HLA-G, fitting with a principal role of LILRB1 in fetal tolerance.
PMID: 29528338
Full text
Article (Published version) (7.3 MB) - public document Free access
Research groups Quorom-sensing et gènes de virulence (301)
Transplantation immunologie et osteoimmunologie (561)
(ISO format)
YU, Kang et al. LILRB1 polymorphisms influence posttransplant HCMV susceptibility and ligand interactions. In: Journal of Clinical Investigation, 2018, vol. 128, n° 4, p. 1523-1537. doi: 10.1172/JCI96174 https://archive-ouverte.unige.ch/unige:111074

345 hits



Deposited on : 2018-11-21

Export document
Format :
Citation style :