Differentiation and activation of human CD4 T cells is associated with a gradual loss of myelin and lymphocyte protein
© 2021 The Authors. European Journal of Immunology published by Wiley-VCH GmbH..
Upon generation of monoclonal antibodies to the T cell antigen receptor/CD3 (TCR/CD3) complex, we isolated mAb MT3, whose reactivity correlates inversely with the production of IFN-γ by human peripheral blood T lymphocytes. Using eukaryotic expression cloning, we identified the MT3 antigen as myelin-and-lymphocyte (MAL) protein. Flow cytometry analysis demonstrates high surface expression of MAL on all naïve CD4+ T cells whereas MAL expression is diminished on central memory- and almost lost on effector memory T cells. MAL- T cells proliferate strongly in response to stimulation with CD3/CD28 antibodies, corroborating that MAL+ T cells are naïve and MAL- T cells memory subtypes. Further, resting MAL- T cells harbor a larger pool of Ser59- and Tyr394- double phosphorylated lymphocyte-specific kinase (Lck), which is rapidly increased upon in vitro restimulation. Previously, lack of MAL was reported to prevent transport of Lck, the key protein tyrosine kinase of TCR/CD3 signaling to the cell membrane, and to result in strongly impaired human T cell activation. Here, we show that knocking out MAL did not significantly affect Lck membrane localization and immune synapse recruitment, or transcriptional T cell activation. Collectively, our results indicate that loss of MAL is associated with activation-induced differentiation of human T cells but not with impaired membrane localization of Lck or TCR signaling capacity.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:51 |
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| Enthalten in: |
European journal of immunology - 51(2021), 4 vom: 15. Apr., Seite 848-863 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Leitner, Judith [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 20.09.2021 Date Revised 12.10.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/eji.202048603 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM319101622 |
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| 100 | 1 | |a Leitner, Judith |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Differentiation and activation of human CD4 T cells is associated with a gradual loss of myelin and lymphocyte protein |
| 264 | 1 | |c 2021 | |
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| 500 | |a Date Revised 12.10.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2021 The Authors. European Journal of Immunology published by Wiley-VCH GmbH. | ||
| 520 | |a Upon generation of monoclonal antibodies to the T cell antigen receptor/CD3 (TCR/CD3) complex, we isolated mAb MT3, whose reactivity correlates inversely with the production of IFN-γ by human peripheral blood T lymphocytes. Using eukaryotic expression cloning, we identified the MT3 antigen as myelin-and-lymphocyte (MAL) protein. Flow cytometry analysis demonstrates high surface expression of MAL on all naïve CD4+ T cells whereas MAL expression is diminished on central memory- and almost lost on effector memory T cells. MAL- T cells proliferate strongly in response to stimulation with CD3/CD28 antibodies, corroborating that MAL+ T cells are naïve and MAL- T cells memory subtypes. Further, resting MAL- T cells harbor a larger pool of Ser59- and Tyr394- double phosphorylated lymphocyte-specific kinase (Lck), which is rapidly increased upon in vitro restimulation. Previously, lack of MAL was reported to prevent transport of Lck, the key protein tyrosine kinase of TCR/CD3 signaling to the cell membrane, and to result in strongly impaired human T cell activation. Here, we show that knocking out MAL did not significantly affect Lck membrane localization and immune synapse recruitment, or transcriptional T cell activation. Collectively, our results indicate that loss of MAL is associated with activation-induced differentiation of human T cells but not with impaired membrane localization of Lck or TCR signaling capacity | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a CD4 | |
| 650 | 4 | |a Differentiation | |
| 650 | 4 | |a Human | |
| 650 | 4 | |a MAL | |
| 650 | 4 | |a T-cell activation | |
| 650 | 7 | |a CD28 Antigens |2 NLM | |
| 650 | 7 | |a CD3 Complex |2 NLM | |
| 650 | 7 | |a Myelin and Lymphocyte-Associated Proteolipid Proteins |2 NLM | |
| 650 | 7 | |a Receptors, Antigen, T-Cell |2 NLM | |
| 650 | 7 | |a Tumor Necrosis Factor-alpha |2 NLM | |
| 650 | 7 | |a Interferon-gamma |2 NLM | |
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| 650 | 7 | |a Lymphocyte Specific Protein Tyrosine Kinase p56(lck) |2 NLM | |
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| 700 | 1 | |a Mahasongkram, Kodchakorn |e verfasserin |4 aut | |
| 700 | 1 | |a Schatzlmaier, Philipp |e verfasserin |4 aut | |
| 700 | 1 | |a Pfisterer, Karin |e verfasserin |4 aut | |
| 700 | 1 | |a Leksa, Vladimir |e verfasserin |4 aut | |
| 700 | 1 | |a Pata, Supansa |e verfasserin |4 aut | |
| 700 | 1 | |a Kasinrerk, Watchara |e verfasserin |4 aut | |
| 700 | 1 | |a Stockinger, Hannes |e verfasserin |4 aut | |
| 700 | 1 | |a Steinberger, Peter |e verfasserin |4 aut | |
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