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Differentiation and activation of human CD4 T cells is associated with a gradual loss of myelin and lymphocyte protein
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Metadata
Document Title
Differentiation and activation of human CD4 T cells is associated with a gradual loss of myelin and lymphocyte protein
Author
Leitner J.,Mahasongkram K.,Schatzlmaier P.,Pfisterer K.,Leksa V.,Pata S.,Kasinrerk W.,Stockinger H.,Steinberger P.
Name from Authors Collection
Affiliations
Division of Immune Receptors and T Cell Activation, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria; Division of Clinical Immunology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand; Institute for Hygiene and Applied Immunology, Centre for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria; Department of Dermatology, Medical University of Vienna, Vienna, Austria; Laboratory of Molecular Immunology, Institute of Molecular Biology, Slovak Academy of Sciences, Bratislava, Slovakia; Biomedical Technology Research Centre, National Centre for Genetic Engineering and Biotechnology, National Science and Technology Development Agency at the Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand
Type
Article
Source Title
European Journal of Immunology
ISSN
00142980
Year
2021
Volume
51
Issue
4
Page
848-863
Open Access
All Open Access, Hybrid Gold, Green
Publisher
John Wiley and Sons Inc
DOI
10.1002/eji.202048603
Abstract
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. © 2021 The Authors. European Journal of Immunology published by Wiley-VCH GmbH
Keyword
CD4 | Differentiation | Human | MAL | T-cell activation
Industrial Classification
Knowledge Taxonomy Level 1
Knowledge Taxonomy Level 2
Knowledge Taxonomy Level 3
License
CC BY
Rights
Author
Publication Source
Scopus