Immobilization of glycosylphosphatidylinositol-anchored proteins inhibits T cell growth but not function
| Autor: | Pamela S. Ohashi, Mina D. Marmor, Martin F. Bachmann, Michael Julius, Thomas R. Malek |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Glycosylphosphatidylinositols
T-Lymphocytes T cell Immunology Cellular homeostasis Mice Transgenic CD48 Antigen Lymphocyte Activation Cell Line Mice Antibody Specificity Antigens CD medicine Animals Antigens Ly Immunology and Allergy Cytotoxic T cell Phosphorylation Receptor Cells Cultured Mice Inbred BALB C Chemistry Effector Antibodies Monoclonal Janus Kinase 3 Membrane Proteins Receptors Interleukin-2 Janus Kinase 1 General Medicine CD48 Protein-Tyrosine Kinases Molecular biology Cell biology medicine.anatomical_structure Receptor-CD3 Complex Antigen T-Cell Thy-1 Antigens Signal transduction Carrier Proteins Janus kinase T-Lymphocytes Cytotoxic |
| Popis: | Accumulating evidence suggests that proteins tethered to the plasma membrane through glycosylphosphatidylinositol (GPI) anchors share common biological properties. In the present study we demonstrate that GPI-anchored proteins regulate T cell growth. Specifically, anti-TCR-induced proliferation was profoundly inhibited by co-immobilized mAb specific for Thy-1, CD48 and Ly6A/E. However, neither IL-2 production nor the effector function of cytotoxic T lymphocytes was impaired in these circumstances. Analysis of the IL-2 receptor (IL-2R) signaling pathway revealed that the association of IL-2R beta and gamma chains with the Janus kinases, JAK1 and JAK3, was not perturbed in the presence of mAb specific for GPI-linked proteins. However, in these conditions, IL-2-mediated recruitment of IL-2Ralpha, beta and gamma chains, resulting in the formation of the high-affinity hetero-trimeric IL-2R, was inhibited. The resulting phosphorylation of JAK1 and JAK3, indicative of their activation states, was correspondingly reduced. These results characterize a novel state of T cell physiology in which effector function is maintained, in the absence of clonal expansion. A physiological role for GPI-anchored proteins in the maintenance of cellular homeostasis and function is discussed. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|