Allele-specific recognition by LILRB3 and LILRA6 of a cytokeratin 8-associated ligand on necrotic glandular epithelial cells.
Jones, Des C
Hewitt, Colin RA
López-Álvarez, María R
Russell, Alasdair I
Trowsdale, Alice RZ
Impact Journals LLC
MetadataShow full item record
Jones, D. C., Hewitt, C. R., López-Álvarez, M. R., Jahnke, M., Russell, A. I., Radjabova, V., Trowsdale, A. R., & et al. (2016). Allele-specific recognition by LILRB3 and LILRA6 of a cytokeratin 8-associated ligand on necrotic glandular epithelial cells.. Oncotarget, 7 (13), 15618-15631. https://doi.org/10.18632/oncotarget.6905
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 responses within the tumour microenvironment. Since LILRB3 and LILRA6 genes are highly polymorphic the interaction may influence an individual's immune response to tumours.
DAMP, LILR, breast cancer, cytokeratin, immune escape, Alleles, Antigens, CD, Cell Line, Epithelial Cells, Humans, Keratin-8, Necrosis, Polymorphism, Single Nucleotide, Receptors, Immunologic
DCJ and JT are funded by Worldwide Cancer Research (formerly the AICR), project grant number 13-0074. Additional funding was provided by grants from the MRC (G0901682) and Wellcome Trust (094207 and 089821). MRL-A was funded by Ministerio de Educación of Spain, under the program “Programa Nacional de Movilidad de Recursos Humanos del Plan Nacional de I-D+i 2008-2011” and Fundación Séneca 04087/GERM/06 Project.
Worldwide Cancer Research (13-0074)
External DOI: https://doi.org/10.18632/oncotarget.6905
This record's URL: https://www.repository.cam.ac.uk/handle/1810/253223
Attribution 4.0 International
Licence URL: http://creativecommons.org/licenses/by/4.0/