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International Immunology Advance Access originally published online on January 15, 2009
International Immunology 2009 21(3):245-255; doi:10.1093/intimm/dxn144
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© The Japanese Society for Immunology. 2009. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

NKp44 expression, phylogenesis and function in non-human primate NK cells

Andrea De Maria1,2,3,*, Elisabetta Ugolotti4,*, Erik Rutjens5,12, Stefania Mazza6,13, Luana Radic4, Alessandro Faravelli4, Gerrit Koopman5, Eddi Di Marco7, Paola Costa1,8, Barbara Ensoli9, Aurelio Cafaro9, Maria Cristina Mingari6,10, Lorenzo Moretta1,6,8, Jonathan Heeney5,11 and Roberto Biassoni4

1 Centro di Eccellenza per la Ricerca Biomedica, Genova, Italy
2 Dipartimento di Medicina Interna, Università di Genova, Genova, Italy
3 S.S. Infettivologia, Istituto Nazionale per la Ricerca sul Cancro, IST-GE
4 Laboratorio Medicina Molecolare, Dipartimento Medicina Sperimentale e di Laboratorio, Istituto Scientifico Giannina Gaslini, Genova, Italy
5 Biomedical Primate Research Centre, Rijswijk, The Netherlands
6 Dipartimento di Medicina Sperimentale, Università di Genova, Genova, Italy
7 Laboratorio Centrale Analisi, Dipartimento Medicina Sperimentale e di Laboratorio, Istituto Scientifico Giannina Gaslini, Genova, Italy
8 Laboratorio Immunologia Clinica e Sperimentale, Dipartimento Medicina Sperimentale e di Laboratorio, Istituto Scientifico Giannina Gaslini, Genova, Italy
9 National AIDS Centre, Istituto Superiore di Sanità, Rome, Italy
10 S.C. Immunologia, Istituto Nazionale per la Ricerca sul Cancro, IST-GE
11 Department of Veterinary Medicine, University of Cambridge, CB3-0ES Cambridge, UK
12 Present address: Pharmacell, Maastricht, The Netherlands
13 Present address: BD Biosciences, Buccinasco (MI), Italy

Correspondence to: R. Biassoni; Medicina Molecolare, Istituto Scientifico Giannina Gaslini, Largo G. Gaslini 5, 16147 Genova, Italy. E-mail: robertobiassoni{at}ospedale-gaslini.ge.it

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.

Keywords: cytotoxicity, evolution, molecular biology, natural cytotoxicity receptors

* These authors contributed equally to this study.

Transmitting editor: S. Romagnani

Received 10 July 2008, accepted 8 December 2008.


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