Proteomic definition of human mucosal-associated invariant T cells determines their unique molecular effector phenotype

European Journal of Immunology
Björn BulittaLothar Jänsch

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 complement...Continue Reading

References

Oct 16, 1999·Proceedings of the National Academy of Sciences of the United States of America·R J BoadoW M Pardridge
Jan 6, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·T J SayersJ M Kelley
Nov 8, 2001·Trends in Immunology·M A CooperM A Caligiuri
Dec 12, 2001·Molecular Biology of the Cell·M N CordonnierE Coudrier
May 3, 2003·Annals of the New York Academy of Sciences·Michael L Dustin
Nov 18, 2003·The Journal of Biological Chemistry·Jiale He, Linda G Baum
Mar 19, 2004·The Journal of Biological Chemistry·Janice M KellyMark J Smyth
Mar 23, 2004·Annual Review of Immunology·Federica SallustoAntonio Lanzavecchia
Sep 24, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·James M MasonCharles C Chu
Sep 24, 2004·Molecular & Cellular Proteomics : MCP·Philip L RossDarryl J Pappin
Jan 6, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Brianna N StillmanLinda G Baum
May 19, 2007·American Journal of Clinical Pathology·William G Morice
May 20, 2008·Cellular and Molecular Life Sciences : CMLS·B SjöblomK Djinović-Carugo
Jul 15, 2009·Immunological Reviews·Daniel K HsuFu-Tong Liu
Feb 6, 2010·Proceedings of the National Academy of Sciences of the United States of America·Eva BillerbeckPaul Klenerman
Jun 12, 2010·Immunological Reviews·Michael L Dustin, Eric O Long
Jun 29, 2010·Nature Immunology·Lionel Le BourhisOlivier Lantz
Jun 30, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Desiree A AnthonyMark J Smyth
Jul 9, 2010·PLoS Biology·Marielle C GoldDavid M Lewinsohn
Oct 12, 2012·Nature·Lars Kjer-NielsenJames McCluskey
Dec 21, 2012·Blood·Cormac CosgrovePaul Klenerman
Jan 15, 2013·Molecular & Cellular Proteomics : MCP·Maxi ScheiterLothar Jänsch
Feb 21, 2013·Current Opinion in Immunology·Lionel Le BourhisOlivier Lantz
Sep 17, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Keitaro HayashiNaohiko Anzai
Oct 9, 2013·The Journal of Experimental Medicine·Rangsima ReantragoonLars Kjer-Nielsen
Oct 17, 2013·PLoS Pathogens·Lionel Le BourhisOlivier Lantz
Nov 5, 2013·Cell Death and Differentiation·S A H de PootN Bovenschen
Jan 15, 2014·Cell Death and Differentiation·S A H de Poot, N Bovenschen
Mar 15, 2014·Cell Death & Disease·N BaschukD M Andrews
May 6, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Laurent Gapin

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Citations

Nov 10, 2018·Frontiers in Microbiology·Isabel BernalLothar Jänsch
Jul 25, 2019·Cells·Valérie Molinier-FrenkelFlavia Castellano
Dec 18, 2020·Frontiers in Immunology·Ali AminiPaul Klenerman
Jul 22, 2020·Current Cancer Drug Targets·Sara IranparastBahman Yousefi

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