title: NKp44 expression, phylogenesis and function in non-human primate NK cells.
abstract: Molecular and functional characterization of the natural cytotoxicity receptor (NCR) NKp44 in species other than Homo sapiens has been elusive, so far. Here, we provide complete phenotypic, molecular and functional characterization for NKp44 triggering receptor on Pan troglodytes NK cells, the closest human relative, and the analysis of NKp44-genomic locus and transcription in Macaca fascicularis. Similar to H. sapiens, NKp44 expression is detectable on chimpanzee NK cells only upon activation. However, basal NKp44 transcription is 5-fold higher in chimpanzees with lower differential increases upon cell activation compared with humans. Upon activation, an overall 12-fold lower NKp44 gene expression is observed in P. troglodytes compared with H. sapiens NK cells with only a slight reduction in NKp44 surface expression. Functional analysis of 'in vitro' activated purified NK cells confirms the NKp44 triggering potential compared with other major NCRs. These findings suggest the presence of a post-transcriptional regulation that evolved differently in H. sapiens. Analysis of cynomolgus NKp44-genomic sequence and transcription pattern showed very low levels of transcription with occurrence of out-of-frame transcripts and no surface expression. The present comparative analysis suggests that NKp44-genomic organization appears during macaque speciation, with considerable evolution of its transcriptional and post-transcriptional tuning. Thus, NKp44 may represent an NCR being only recently emerged during speciation, acquiring functional relevance only in non-human primates closest to H. sapiens.
authors.affiliation: Centro di Eccellenza per la Ricerca Biomedica, Genova, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: De Maria
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Ugolotti
authors.forename: Erik
authors.initials: E
authors.lastname: Rutjens
authors.forename: Stefania
authors.initials: S
authors.lastname: Mazza
authors.forename: Luana
authors.initials: L
authors.lastname: Radic
authors.forename: Alessandro
authors.initials: A
authors.lastname: Faravelli
authors.forename: Gerrit
authors.initials: G
authors.lastname: Koopman
authors.forename: Eddi
authors.initials: E
authors.lastname: Di Marco
authors.forename: Paola
authors.initials: P
authors.lastname: Costa
authors.forename: Barbara
authors.initials: B
authors.lastname: Ensoli
authors.forename: Aurelio
authors.initials: A
authors.lastname: Cafaro
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Mingari
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moretta
authors.forename: Jonathan
authors.initials: J
authors.lastname: Heeney
authors.forename: Roberto
authors.initials: R
authors.lastname: Biassoni
mesh_terms: D000818:Animals; D019143:Evolution, Molecular; D016368:Frameshift Mutation / Q000276:immunology; D049810:Genetic Speciation; D006801:Humans; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation; D008252:Macaca fascicularis / Q000276:immunology*; D055629:Natural Cytotoxicity Triggering Receptor 2 / Q000096:biosynthesis / Q000235:genetics*; D002679:Pan troglodytes / Q000276:immunology*; D010802:Phylogeny; D011499:Protein Processing, Post-Translational / Q000276:immunology; D014158:Transcription, Genetic / Q000276:immunology
chemical_list: D055629:Natural Cytotoxicity Triggering Receptor 2