The promiscuous development of an unconventional Qa1b-restricted T cell population
MHC-E restricted CD8 T cells show promise in vaccine settings, but their development and specificity remain poorly understood. Here we focus on a CD8 T cell population reactive to a self-peptide (FL9) bound to mouse MHC-E (Qa-1b) that is presented in response to loss of the MHC I processing enzyme E...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-10-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1250316/full |
| _version_ | 1797644331102765056 |
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| author | Michael Manoharan Valerio Kathya Arana Jian Guan Shiao Wei Chan Xiaokun Yang Nadia Kurd Angus Lee Nilabh Shastri Laurent Coscoy Ellen A. Robey |
| author_facet | Michael Manoharan Valerio Kathya Arana Jian Guan Shiao Wei Chan Xiaokun Yang Nadia Kurd Angus Lee Nilabh Shastri Laurent Coscoy Ellen A. Robey |
| author_sort | Michael Manoharan Valerio |
| collection | DOAJ |
| description | MHC-E restricted CD8 T cells show promise in vaccine settings, but their development and specificity remain poorly understood. Here we focus on a CD8 T cell population reactive to a self-peptide (FL9) bound to mouse MHC-E (Qa-1b) that is presented in response to loss of the MHC I processing enzyme ERAAP, termed QFL T cells. We find that mature QFL thymocytes are predominantly CD8αβ+CD4-, show signs of agonist selection, and give rise to both CD8αα and CD8αβ intraepithelial lymphocytes (IEL), as well as memory phenotype CD8αβ T cells. QFL T cells require the MHC I subunit β-2 microglobulin (β2m), but do not require Qa1b or classical MHC I for positive selection. However, QFL thymocytes do require Qa1b for agonist selection and full functionality. Our data highlight the relaxed requirements for positive selection of an MHC-E restricted T cell population and suggest a CD8αβ+CD4- pathway for development of CD8αα IELs. |
| first_indexed | 2024-03-11T14:28:59Z |
| format | Article |
| id | doaj.art-39ecc32a95a34e96b4b07cd3ca823fbb |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-11T14:28:59Z |
| publishDate | 2023-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-39ecc32a95a34e96b4b07cd3ca823fbb2023-10-31T11:20:54ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-10-011410.3389/fimmu.2023.12503161250316The promiscuous development of an unconventional Qa1b-restricted T cell populationMichael Manoharan Valerio0Kathya Arana1Jian Guan2Shiao Wei Chan3Xiaokun Yang4Nadia Kurd5Angus Lee6Nilabh Shastri7Laurent Coscoy8Ellen A. Robey9Division of Immunology and Molecular Medicine, Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA, United StatesDivision of Immunology and Molecular Medicine, Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA, United StatesDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesDivision of Immunology and Molecular Medicine, Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA, United StatesDivision of Immunology and Molecular Medicine, Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA, United StatesDivision of Immunology and Molecular Medicine, Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA, United StatesGene Targeting Facility Cancer Research Laboratory, University of California Berkeley, Berkeley, CA, United StatesDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesDivision of Immunology and Molecular Medicine, Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA, United StatesDivision of Immunology and Molecular Medicine, Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA, United StatesMHC-E restricted CD8 T cells show promise in vaccine settings, but their development and specificity remain poorly understood. Here we focus on a CD8 T cell population reactive to a self-peptide (FL9) bound to mouse MHC-E (Qa-1b) that is presented in response to loss of the MHC I processing enzyme ERAAP, termed QFL T cells. We find that mature QFL thymocytes are predominantly CD8αβ+CD4-, show signs of agonist selection, and give rise to both CD8αα and CD8αβ intraepithelial lymphocytes (IEL), as well as memory phenotype CD8αβ T cells. QFL T cells require the MHC I subunit β-2 microglobulin (β2m), but do not require Qa1b or classical MHC I for positive selection. However, QFL thymocytes do require Qa1b for agonist selection and full functionality. Our data highlight the relaxed requirements for positive selection of an MHC-E restricted T cell population and suggest a CD8αβ+CD4- pathway for development of CD8αα IELs.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1250316/fullMHC-ET cell developmentunconventional T cellsnon-classical MHC-1IEL |
| spellingShingle | Michael Manoharan Valerio Kathya Arana Jian Guan Shiao Wei Chan Xiaokun Yang Nadia Kurd Angus Lee Nilabh Shastri Laurent Coscoy Ellen A. Robey The promiscuous development of an unconventional Qa1b-restricted T cell population Frontiers in Immunology MHC-E T cell development unconventional T cells non-classical MHC-1 IEL |
| title | The promiscuous development of an unconventional Qa1b-restricted T cell population |
| title_full | The promiscuous development of an unconventional Qa1b-restricted T cell population |
| title_fullStr | The promiscuous development of an unconventional Qa1b-restricted T cell population |
| title_full_unstemmed | The promiscuous development of an unconventional Qa1b-restricted T cell population |
| title_short | The promiscuous development of an unconventional Qa1b-restricted T cell population |
| title_sort | promiscuous development of an unconventional qa1b restricted t cell population |
| topic | MHC-E T cell development unconventional T cells non-classical MHC-1 IEL |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1250316/full |
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