Expression of CD226 is Associated to but Not Required for NK Cell Education

Overview

Journal Nat Commun

Specialty Biology

Date 2017 Jun 1

PMID 28561023

Citations 29

Authors

Arnika K Wagner

Nadir Kadri

Johanna Snall

Petter Brodin

Susan Gilfillan

Marco Colonna

Gunter Bernhardt

Petter Hoglund

Klas Karre

Benedict J Chambers

Affiliations

Soon will be listed here.

Abstract

DNAX accessory molecule-1 (DNAM-1, also known as CD226) is an activating receptor expressed on subsets of natural killer (NK) and T cells, interacts with its ligands CD155 or CD112, and has co-varied expression with inhibitory receptors. Since inhibitory receptors control NK-cell activation and are necessary for MHC-I-dependent education, we investigated whether DNAM-1 expression is also involved in NK-cell education. Here we show an MHC-I-dependent correlation between DNAM-1 expression and NK-cell education, and an association between DNAM-1 and NKG2A that occurs even in MHC class I deficient mice. DNAM-1 is expressed early during NK-cell development, precedes the expression of MHC-I-specific inhibitory receptors, and is modulated in an education-dependent fashion. Cd226 mice have missing self-responses and NK cells with a normal receptor repertoire. We propose a model in which NK-cell education prevents or delays downregulation of DNAM-1. This molecule endows educated NK cells with enhanced effector functions but is dispensable for education.

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References

Enqvist M, Ask E, Forslund E, Carlsten M, Abrahamsen G, Beziat V . Coordinated expression of DNAM-1 and LFA-1 in educated NK cells. J Immunol. 2015; 194(9):4518-27. DOI: 10.4049/jimmunol.1401972. View

Iguchi-Manaka A, Kai H, Yamashita Y, Shibata K, Tahara-Hanaoka S, Honda S . Accelerated tumor growth in mice deficient in DNAM-1 receptor. J Exp Med. 2008; 205(13):2959-64. PMC: 2605241. DOI: 10.1084/jem.20081611. View

Michaelsson J, Achour A, Salcedo M, Sundback J, Harris R, Karre K . Visualization of inhibitory Ly49 receptor specificity with soluble major histocompatibility complex class I tetramers. Eur J Immunol. 1999; 30(1):300-7. DOI: 10.1002/1521-4141(200001)30:1<300::AID-IMMU300>3.0.CO;2-S. View

Corral L, Hanke T, VANCE R, Cado D, Raulet D . NK cell expression of the killer cell lectin-like receptor G1 (KLRG1), the mouse homolog of MAFA, is modulated by MHC class I molecules. Eur J Immunol. 2000; 30(3):920-30. DOI: 10.1002/1521-4141(200003)30:3<920::AID-IMMU920>3.0.CO;2-P. View

Brodin P, Lakshmikanth T, Johansson S, Karre K, Hoglund P . The strength of inhibitory input during education quantitatively tunes the functional responsiveness of individual natural killer cells. Blood. 2008; 113(11):2434-41. DOI: 10.1182/blood-2008-05-156836. View

Seth S, Georgoudaki A, Chambers B, Qiu Q, Kremmer E, Maier M . Heterogeneous expression of the adhesion receptor CD226 on murine NK and T cells and its function in NK-mediated killing of immature dendritic cells. J Leukoc Biol. 2009; 86(1):91-101. DOI: 10.1189/jlb.1208745. View

Joncker N, Shifrin N, Delebecque F, Raulet D . Mature natural killer cells reset their responsiveness when exposed to an altered MHC environment. J Exp Med. 2010; 207(10):2065-72. PMC: 2947079. DOI: 10.1084/jem.20100570. View

Carlsten M, Norell H, Bryceson Y, Poschke I, Schedvins K, Ljunggren H . Primary human tumor cells expressing CD155 impair tumor targeting by down-regulating DNAM-1 on NK cells. J Immunol. 2009; 183(8):4921-30. DOI: 10.4049/jimmunol.0901226. View

Shibuya A, Campbell D, Hannum C, Yssel H, McClanahan T, Kitamura T . DNAM-1, a novel adhesion molecule involved in the cytolytic function of T lymphocytes. Immunity. 1996; 4(6):573-81. DOI: 10.1016/s1074-7613(00)70060-4. View

10.

VANCE R, KRAFT J, Altman J, Jensen P, Raulet D . Mouse CD94/NKG2A is a natural killer cell receptor for the nonclassical major histocompatibility complex (MHC) class I molecule Qa-1(b). J Exp Med. 1998; 188(10):1841-8. PMC: 2212405. DOI: 10.1084/jem.188.10.1841. View

11.

Braud V, Allan D, OCallaghan C, Soderstrom K, DAndrea A, Ogg G . HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C. Nature. 1998; 391(6669):795-9. DOI: 10.1038/35869. View

12.

Roth C, Carlyle J, Takizawa H, Raulet D . Clonal acquisition of inhibitory Ly49 receptors on developing NK cells is successively restricted and regulated by stromal class I MHC. Immunity. 2000; 13(1):143-53. DOI: 10.1016/s1074-7613(00)00015-7. View

13.

Sivakumar P, Gunturi A, Salcedo M, Schatzle J, Lai W, Kurepa Z . Cutting edge: expression of functional CD94/NKG2A inhibitory receptors on fetal NK1.1+Ly-49- cells: a possible mechanism of tolerance during NK cell development. J Immunol. 1999; 162(12):6976-80. View

14.

Raulet D, HELD W, Correa I, Dorfman J, Wu M, Corral L . Specificity, tolerance and developmental regulation of natural killer cells defined by expression of class I-specific Ly49 receptors. Immunol Rev. 1997; 155:41-52. DOI: 10.1111/j.1600-065x.1997.tb00938.x. View

15.

Viant C, Fenis A, Chicanne G, Payrastre B, Ugolini S, Vivier E . SHP-1-mediated inhibitory signals promote responsiveness and anti-tumour functions of natural killer cells. Nat Commun. 2014; 5:5108. DOI: 10.1038/ncomms6108. View

16.

Nabekura T, Kanaya M, Shibuya A, Fu G, Gascoigne N, Lanier L . Costimulatory molecule DNAM-1 is essential for optimal differentiation of memory natural killer cells during mouse cytomegalovirus infection. Immunity. 2014; 40(2):225-34. PMC: 3943894. DOI: 10.1016/j.immuni.2013.12.011. View

17.

Peterson M, Long E . Inhibitory receptor signaling via tyrosine phosphorylation of the adaptor Crk. Immunity. 2008; 29(4):578-88. PMC: 2639764. DOI: 10.1016/j.immuni.2008.07.014. View

18.

Fuchs A, Colonna M . The role of NK cell recognition of nectin and nectin-like proteins in tumor immunosurveillance. Semin Cancer Biol. 2006; 16(5):359-66. DOI: 10.1016/j.semcancer.2006.07.002. View

19.

Hayakawa Y, Smyth M . CD27 dissects mature NK cells into two subsets with distinct responsiveness and migratory capacity. J Immunol. 2006; 176(3):1517-24. DOI: 10.4049/jimmunol.176.3.1517. View

20.

Martinet L, Ferrari de Andrade L, Guillerey C, Lee J, Liu J, Souza-Fonseca-Guimaraes F . DNAM-1 expression marks an alternative program of NK cell maturation. Cell Rep. 2015; 11(1):85-97. DOI: 10.1016/j.celrep.2015.03.006. View