LILRB1 polymorphisms influence posttransplant HCMV susceptibility and ligand interactions.

Yu, Kang; Davidson, Chelsea L; Wójtowicz, Agnieszka; Lisboa, Luiz; Wang, Ting; Airo, Adriana M; Villard, Jean; Buratto, Jeremie; Sandalova, Tatyana; Achour, Adnane; Humar, Atul; Boggian, Katia; Cusini, Alexia; van Delden, Christian; Egli, Adrian; Manuel, Oriol; Mueller, Nicolas; Bochud, Pierre-Yves; Burshtyn, Deborah N (2018). LILRB1 polymorphisms influence posttransplant HCMV susceptibility and ligand interactions. Journal of clinical investigation, 128(4), pp. 1523-1537. American Society for Clinical Investigation 10.1172/JCI96174

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Infectiology

UniBE Contributor:

Cusini, Alexia

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0021-9738

Publisher:

American Society for Clinical Investigation

Language:

English

Submitter:

Annelies Luginbühl

Date Deposited:

25 Apr 2018 09:18

Last Modified:

05 Sep 2018 17:33

Publisher DOI:

10.1172/JCI96174

PubMed ID:

29528338

Uncontrolled Keywords:

Genetic variation Immunology Infectious disease Innate immunity Organ transplantation

BORIS DOI:

10.7892/boris.113308

URI:

https://boris.unibe.ch/id/eprint/113308

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