Formation and Function of the Lytic NK-cell Immunological Synapse

Overview

Journal Nat Rev Immunol

Specialty Allergy & Immunology

Date 2009 Jan 28

PMID 19172692

Citations 316

Authors

Jordan S Orange

Affiliations

Soon will be listed here.

Abstract

The natural killer (NK)-cell immunological synapse is the dynamic interface formed between an NK cell and its target cell. Formation of the NK-cell immunological synapse involves several distinct stages, from the initiation of contact with a target cell to the directed delivery of lytic-granule contents for target-cell lysis. Progression through the individual stages is regulated, and this tight regulation underlies the precision with which NK cells select and kill susceptible target cells (including virally infected cells and cancerous cells) that they encounter during their routine surveillance of the body.

Citing Articles

Single-chain variable fragment affinity tuning can optimize anti-AML CAR-NK cell functionality.

Rahnama R, Kizerwetter M, Yang H, Christodoulou I, Guaraca C, Holl N J Immunother Cancer. 2025; 13(2).

PMID: 39915004 PMC: 11804205. DOI: 10.1136/jitc-2024-010763.

Tumor cells escape immunosurveillance by hampering LFA-1.

Upadhyay S, Murugu L, Svensson L Front Immunol. 2025; 16:1519841.

PMID: 39911389 PMC: 11794523. DOI: 10.3389/fimmu.2025.1519841.

A framework integrating multiscale in-silico modeling and experimental data predicts CD33CAR-NK cytotoxicity across target cell types.

Ahmad S, Xing K, Rajakaruna H, Stewart W, Beckwith K, Nayak I bioRxiv. 2025; .

PMID: 39803543 PMC: 11722217. DOI: 10.1101/2024.12.31.630941.

Development of BCMA-Targeted Bispecific Natural Killer Cell Engagers for Multiple Myeloma Treatment.

Zhang M, Loh H, Goh Fang S, Yang Y, Lam K, Xu S Antibodies (Basel). 2024; 13(4).

PMID: 39727480 PMC: 11672634. DOI: 10.3390/antib13040097.

Ontogeny and function of the intestinal epithelial and innate immune cells during early development of chicks: to explore in ovo immunomodulatory nutrition.

Ayalew H, Xu C, Adane A, Sanchez A, Li S, Wang J Poult Sci. 2024; 104(1):104607.

PMID: 39693955 PMC: 11720616. DOI: 10.1016/j.psj.2024.104607.

References

Lou Z, Jevremovic D, Billadeau D, Leibson P . A balance between positive and negative signals in cytotoxic lymphocytes regulates the polarization of lipid rafts during the development of cell-mediated killing. J Exp Med. 2000; 191(2):347-54. PMC: 2195747. DOI: 10.1084/jem.191.2.347. View

Purbhoo M, Irvine D, Huppa J, Davis M . T cell killing does not require the formation of a stable mature immunological synapse. Nat Immunol. 2004; 5(5):524-30. DOI: 10.1038/ni1058. View

Wang I, Lu M, Chiang B, Lin W, Lin D, Lin K . Epstein-Barr virus associated post-transplantation lymphoproliferative disorder with hemophagocytosis in a child with Wiskott-Aldrich syndrome. Pediatr Blood Cancer. 2004; 45(3):340-3. DOI: 10.1002/pbc.20191. View

Sullivan K, Mullen C, Blaese R, Winkelstein J . A multiinstitutional survey of the Wiskott-Aldrich syndrome. J Pediatr. 1994; 125(6 Pt 1):876-85. DOI: 10.1016/s0022-3476(05)82002-5. View

Hanna J, Gonen-Gross T, Fitchett J, Rowe T, Daniels M, Arnon T . Novel APC-like properties of human NK cells directly regulate T cell activation. J Clin Invest. 2004; 114(11):1612-23. PMC: 529284. DOI: 10.1172/JCI22787. View

Reczek D, Schwake M, Schroder J, Hughes H, Blanz J, Jin X . LIMP-2 is a receptor for lysosomal mannose-6-phosphate-independent targeting of beta-glucocerebrosidase. Cell. 2007; 131(4):770-83. DOI: 10.1016/j.cell.2007.10.018. View

Feldmann J, Callebaut I, Raposo G, Certain S, Bacq D, Dumont C . Munc13-4 is essential for cytolytic granules fusion and is mutated in a form of familial hemophagocytic lymphohistiocytosis (FHL3). Cell. 2003; 115(4):461-73. DOI: 10.1016/s0092-8674(03)00855-9. View

Inoue H, Miyaji M, Kosugi A, Nagafuku M, Okazaki T, Mimori T . Lipid rafts as the signaling scaffold for NK cell activation: tyrosine phosphorylation and association of LAT with phosphatidylinositol 3-kinase and phospholipase C-gamma following CD2 stimulation. Eur J Immunol. 2002; 32(8):2188-98. DOI: 10.1002/1521-4141(200208)32:8<2188::AID-IMMU2188>3.0.CO;2-T. View

Stinchcombe J, Bossi G, Booth S, Griffiths G . The immunological synapse of CTL contains a secretory domain and membrane bridges. Immunity. 2001; 15(5):751-61. DOI: 10.1016/s1074-7613(01)00234-5. View

10.

Barral D, Ramalho J, Anders R, Hume A, Knapton H, Tolmachova T . Functional redundancy of Rab27 proteins and the pathogenesis of Griscelli syndrome. J Clin Invest. 2002; 110(2):247-57. PMC: 151050. DOI: 10.1172/JCI15058. View

11.

Gismondi A, Jacobelli J, Mainiero F, Paolini R, Piccoli M, Frati L . Cutting edge: functional role for proline-rich tyrosine kinase 2 in NK cell-mediated natural cytotoxicity. J Immunol. 2000; 164(5):2272-6. DOI: 10.4049/jimmunol.164.5.2272. View

12.

Davis D, Chiu I, Fassett M, COHEN G, Mandelboim O, Strominger J . The human natural killer cell immune synapse. Proc Natl Acad Sci U S A. 1999; 96(26):15062-7. PMC: 24773. DOI: 10.1073/pnas.96.26.15062. View

13.

Carpen O, Virtanen I, Lehto V, Saksela E . Polarization of NK cell cytoskeleton upon conjugation with sensitive target cells. J Immunol. 1983; 131(6):2695-8. View

14.

Bryceson Y, March M, Barber D, Ljunggren H, Long E . Cytolytic granule polarization and degranulation controlled by different receptors in resting NK cells. J Exp Med. 2005; 202(7):1001-12. PMC: 2213171. DOI: 10.1084/jem.20051143. View

15.

Zur Stadt U, Beutel K, Kolberg S, Schneppenheim R, Kabisch H, Janka G . Mutation spectrum in children with primary hemophagocytic lymphohistiocytosis: molecular and functional analyses of PRF1, UNC13D, STX11, and RAB27A. Hum Mutat. 2005; 27(1):62-8. DOI: 10.1002/humu.20274. View

16.

Chang J, Palanivel V, Kinjyo I, Schambach F, Intlekofer A, Banerjee A . Asymmetric T lymphocyte division in the initiation of adaptive immune responses. Science. 2007; 315(5819):1687-91. DOI: 10.1126/science.1139393. View

17.

Kishimoto T, Hollander N, Roberts T, Anderson D, Springer T . Heterogeneous mutations in the beta subunit common to the LFA-1, Mac-1, and p150,95 glycoproteins cause leukocyte adhesion deficiency. Cell. 1987; 50(2):193-202. DOI: 10.1016/0092-8674(87)90215-7. View

18.

Gomez T, Kumar K, Medeiros R, Shimizu Y, Leibson P, Billadeau D . Formins regulate the actin-related protein 2/3 complex-independent polarization of the centrosome to the immunological synapse. Immunity. 2007; 26(2):177-90. PMC: 2836258. DOI: 10.1016/j.immuni.2007.01.008. View

19.

Sivori S, Parolini S, Falco M, Marcenaro E, Biassoni R, Bottino C . 2B4 functions as a co-receptor in human NK cell activation. Eur J Immunol. 2000; 30(3):787-93. DOI: 10.1002/1521-4141(200003)30:3<787::AID-IMMU787>3.0.CO;2-I. View

20.

Giurisato E, Cella M, Takai T, Kurosaki T, Feng Y, Longmore G . Phosphatidylinositol 3-kinase activation is required to form the NKG2D immunological synapse. Mol Cell Biol. 2007; 27(24):8583-99. PMC: 2169389. DOI: 10.1128/MCB.01477-07. View