Differentiation and activation of human CD4 T cells is associated with a gradual loss of myelin and lymphocyte protein

Judith Leitner, Kodchakorn Mahasongkram, Philipp Schatzlmaier, Karin Pfisterer, Vladimir Leksa, Supansa Pata, Watchara Kasinrerk, Hannes Stockinger, Peter Steinberger

Research output: Journal article (peer-reviewed)Journal article

5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)848-863
Number of pages16
JournalEuropean Journal of Immunology
Volume51
Issue number4
DOIs
Publication statusPublished - Apr 2021
Externally publishedYes

Keywords

  • Animals
  • CD28 Antigens/immunology
  • CD3 Complex/immunology
  • CD4-Positive T-Lymphocytes/cytology
  • Cell Differentiation/genetics
  • Cell Line, Tumor
  • Flow Cytometry
  • Gene Expression/immunology
  • Humans
  • Interferon-gamma/immunology
  • Jurkat Cells
  • Lymphocyte Activation/genetics
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/genetics
  • Mice
  • Myelin and Lymphocyte-Associated Proteolipid Proteins/genetics
  • Phosphorylation
  • Receptors, Antigen, T-Cell/genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction/genetics
  • Tumor Necrosis Factor-alpha/immunology

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