Proteomic definition of human mucosal‐associated invariant T cells determines their unique molecular effector phenotype. Issue 8 (30th May 2018)

• Record Type: Journal Article
• Authors: Bulitta, Björn; Zuschratter, Werner; Bernal, Isabel; Bruder, Dunja; Klawonn, Frank; von Bergen, Martin; Garritsen, Henrikus Stephanus Paulus; Jänsch, Lothar
• Is Part Of: European journal of immunology. Volume 48:Issue 8(2018)
• Page Start: 1336
• Page End: 1349
• Publication Date: 2018-05-30
• Subjects: CD8 T cells -- Effector proteins -- Immunological synapse -- MAIT cells -- Proteomics; Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201747398
• Languages: English
• ISSNs: 0014-2980

Abstract

Abstract: Mucosal‐associated invariant T cells (MAIT) constitute the most abundant anti‐bacterial CD8 + T‐cell population in humans. MR1/TCR‐activated MAIT cells were reported to organize cytotoxic and innate‐like responses but knowledge about their molecular effector phenotype is still fragmentary. Here, we have examined the functional inventory of human MAIT cells (CD3 + Vα7.2 + CD161 + ) in comparison with those from conventional non‐MAIT CD8 + T cells (cCD8 + ) and NK cells. Quantitative mass spectrometry characterized 5500 proteins of primary MAIT cells and identified 160 and 135 proteins that discriminate them from cCD8 + T cells and NK cells donor‐independently. Most notably, MAIT cells showed a unique exocytosis machinery in parallel to a proinflammatory granzyme profile with high levels of the granzymes A, K, and M. Furthermore, 24 proteins were identified with highest abundances in MAIT cells, including CD26, CD98, and L‐amino‐oxidase (LAAO). Among those, expression of granzyme K and CD98 were validated as MAIT‐specific with respect to non‐MAIT CD8 + effector subsets and LAAO was found to be recruited together with granzymes, perforin, and CD107a at the immunological synapse of activated MAIT cells. In conclusion, this study complements knowledge on the molecular effector phenotype of MAIT cells and suggest novel immune regulatory functions as part of their cytotoxic responses. Abstract : Mucosal invariant T (MAIT) cells are the highest abundant effector memory T‐cell subset in humans. With proteomics, we compared MAIT cells to CD8 + T and NK cells in healthy individuals and discovered functions, including granzyme K and LAAO, which contribute to their unique anti‐bacterial responsiveness at immunological synapses.