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.

Whilst genes can drive social traits, social traits themselves can create and maintain genetic variation in populations. The resulting underlying genetic variation can shape how individuals respond to challenges (e.g., stress, undernutrition) and/or predict how rapidly populations adapt to changing environments (e.g, climate change, habitat destruction). Here, we investigate how a social behaviour, parental care, can shape molecular genetic variation in the subsocial insect Nicrophorus vespilloides. Using whole genome sequencing of populations that have evolved in the presence or absence of parental care for 30 generations, we show that parental care can increase levels of standing genetic variation. In contrast, under a harsh environment without care, strong directional selection causes a reduction in genetic variation. Furthermore, we show that adaptation to the loss of care is associated with genetic divergence between populations at loci related to stress, morphological development and transcriptional regulation. These data shed light on the genetic processes that shape and maintain genetic diversity in response to parental care within populations and the mechanisms of adaptation to stressors in the face of the extreme loss of care.