Identification of CD245 as myosin 18A, a receptor for surfactant A: A novel pathway for activating human NK lymphocytes

A De Masson; J Giustiniani; A Marie-Cardine; J D Bouaziz; N Dulphy; D Gossot; P Validire; A Tazi; C Garbar; M Bagot; Y Merrouche; A Bensussan

doi:10.1080/2162402X.2015.1127493

Identification of CD245 as myosin 18A, a receptor for surfactant A: A novel pathway for activating human NK lymphocytes

Oncoimmunology. 2016 Jan 13;5(5):e1127493. doi: 10.1080/2162402X.2015.1127493. eCollection 2016 May.

Authors

A De Masson¹, J Giustiniani², A Marie-Cardine³, J D Bouaziz⁴, N Dulphy⁵, D Gossot⁶, P Validire⁷, A Tazi⁸, C Garbar², M Bagot⁴, Y Merrouche², A Bensussan³

Affiliations

¹ Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche Scientifique (UMRS)-976, Laboratoire "Oncodermatology, Immunology and Cutaneous Stem Cells", Hôpital Saint-Louis, Paris, France; Université Paris VII Paris Diderot, Sorbonne Paris Cité, Paris, France; Service de Dermatologie, Hôpital Saint-Louis, Paris, France; Harvard Skin Disease Research Center, Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
² Institut Jean Godinot, Unicancer, Reims, France; Université Reims-Champagne-Ardenne, DERM-I-C, EA7319, 51 rue Cognacq-Jay , Reims cedex, France.
³ Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche Scientifique (UMRS)-976, Laboratoire "Oncodermatology, Immunology and Cutaneous Stem Cells", Hôpital Saint-Louis, Paris, France; Université Paris VII Paris Diderot, Sorbonne Paris Cité, Paris, France.
⁴ Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche Scientifique (UMRS)-976, Laboratoire "Oncodermatology, Immunology and Cutaneous Stem Cells", Hôpital Saint-Louis, Paris, France; Université Paris VII Paris Diderot, Sorbonne Paris Cité, Paris, France; Service de Dermatologie, Hôpital Saint-Louis, Paris, France.
⁵ Université Paris VII Paris Diderot, Sorbonne Paris Cité, Paris, France; INSERM UMRS-1160, Institut Universitaire d'Hématologie, Hôpital Saint-Louis, Paris, France; Laboratoire d'Immunologie et Histocompatibilité, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, Paris, France.
⁶ Service de chirurgie thoracique, Institut Mutualiste Montsouris , Paris, France.
⁷ Service d'anatomopathologie, Institut Mutualiste Montsouris , Paris, France.
⁸ Université Paris VII Paris Diderot, Sorbonne Paris Cité, Paris, France; Service de pneumologie, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, Paris, France.

Abstract

CD245 is a human surface antigen expressed on peripheral blood lymphocytes, initially delineated by two monoclonal antibodies DY12 and DY35. Until now, CD245 molecular and functional characteristics remained largely unknown. We combined immunological and proteomic approaches and identified CD245 as the unconventional myosin 18A, a highly conserved motor enzyme reported as a receptor for the surfactant protein A (SP-A), that plays a critical role in cytoskeleton organization and Golgi budding. We report that the recruitment of CD245 strongly enhanced NK cell cytotoxicity. Further, we show that the enhancement of the NK lymphocytes killing ability toward CD137-ligand expressing target cells could result from the induction of CD137 expression following CD245 engagement. The SP-A receptor could therefore represent a novel and promising target in cancer immunotherapy.

Keywords: Cytotoxicity; NK cell receptor; NK cells; lymphocytes.

Publication types

Research Support, Non-U.S. Gov't