Allele-specific recognition by LILRB3 and LILRA6 of a cytokeratin 8-associated ligand on necrotic glandular epithelial cells

Oncotarget
Des C JonesJohn Trowsdale

Abstract

The LILRs are a family of receptors that regulate the activities of myelomonocytic cells. We found that specific allelic variants of two related members of the LILR family, LILRB3 and LILRA6, interact with a ligand exposed on necrotic glandular epithelial cells. The extracellular domains of LILRB3 and LILRA6 are very similar and their genes are highly polymorphic. A commonly occurring allele, LILRB3*12, displayed particularly strong binding of these necrotic cells and further screening of the products of LILRB3 alleles identified motifs that correlated with binding. Immunoprecipitation of the ligand from epithelial cell lysates using recombinant LILRB3*12, identified cytokeratins 8, 18 and 19. Purified proteins obtained from epithelial cell lysates, using anti-cytokeratin 8 antibodies, were able to activate LILRB3*12 reporter cells. Knock-down of cytokeratin 8 in epithelial cells abrogated expression of the LILRB3 ligand, while staining with recombinant LILRB3*12 showed co-localisation with cytokeratin 8 and 18 in permeabilised breast cancer cells. Necrosis is a common feature of tumours. The finding of a necrosis-associated ligand for these two receptors raises the possibility of a novel interaction that alters immune response...Continue Reading

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Citations

Jun 24, 2016·Immunogenetics·M R López-ÁlvarezJ A Traherne
Jan 10, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yuxi ZhaoAlex J McCarthy
Jun 2, 2020·Frontiers in Immunology·Alexander L Lewis Marffy, Alex J McCarthy
Feb 3, 2021·Journal of Human Genetics·Kouyuki HirayasuRikinari Hanayama
May 1, 2021·Antibody Therapeutics·Mi DengCheng Cheng Zhang

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Methods Mentioned

BETA
flow cytometry
shRNA

Software Mentioned

Dfire
ZEN
Qmean6
Procheck
Raptor
Graphpad
Raptor X

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