Contribution of the SYK Tyrosine kinase expression to human iNKT self‐reactivity. Issue 10 (8th June 2020)

• Record Type: Journal Article
• Authors: Perroteau, Jeanne; Navet, Benjamin; Devilder, Marie‐Claire; Hesnard, Leslie; Scotet, Emmanuel; Gapin, Laurent; Saulquin, Xavier; Gautreau‐Rolland, Laetitia
• Is Part Of: European journal of immunology. Volume 50:Issue 10(2020)
• Page Start: 1454
• Page End: 1467
• Publication Date: 2020-06-08
• Subjects: CD1d -- iNKT cells -- Self‐reactivity -- SYK Tyrosine kinase -- TCR; Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201948416
• Languages: English
• ISSNs: 0014-2980

Abstract

Abstract: Invariant Natural Killer T (iNKT) cells are particular T lymphocytes at the frontier between innate and adaptative immunities. They participate in the elimination of pathogens or tumor cells, but also in the development of allergic reactions and autoimmune diseases. From their first descriptions, the phenomenon of self‐reactivity has been described. Indeed, they are able to recognize exogenous and endogenous lipids. However, the mechanisms underlying the self‐reactivity are still largely unknown, particularly in humans. Using a CD1d tetramer‐based sensitive immunomagnetic approach, we generated self‐reactive iNKT cell lines from blood circulating iNKT cells of healthy donors. Analysis of their functional characteristics in vitro showed that these cells recognized endogenous lipids presented by CD1d molecules through their TCR that do not correspond to α‐glycosylceramides. TCR sequencing and transcriptomic analysis of T cell clones revealed that a particular TCR signature and an expression of the SYK protein kinase were two mechanisms supporting human iNKT self‐reactivity. The SYK expression, strong in the most self‐reactive iNKT clones and variable in ex vivo isolated iNKT cells, seems to decrease the activation threshold of iNKT cells and increase their overall antigenic sensitivity. This study indicates that a modulation of the TCR intracellular signal contributes to iNKT self‐reactivity. Abstract : The expression of the SYK Tyrosine kinase contributes to decrease the activation threshold of iNKT cells and increase their self‐reactivity. This antigenic sensibility is also constrained by the TCR sequence recognizing the self‐lipid/CD1d complex.