Abnormal early TCR/CD3-mediated signaling events of a snRNP-autoreactive lupus T cell clone.
Multiple immunoregulatory abnormalities characterize systemic lupus erythematosus. Abnormalities of the antigen receptor-mediated early signal transduction biochemical events underscore the diverse cellular aberrations. Fresh peripheral T and B cells and T cell lines from patients with systemic lupus erythematosus display increased Ca2+ responses that are preceded by enhanced antigen receptor-initiated cytosolic protein tyrosine phosphorylation. To further dissect the aberrant signaling events of lupus T cells we studied the early anti-CD3 mAb-induced signaling events in autoantigen-specific T cells from lupus patients. We report herein that a lupus snRNP-specific T cell clone, but not other T cells, displays increased Ca2+ fluxes and enhanced production of tyrosine-phosphorylated proteins following TCR/CD3 stimulation.
Liossis
S N
SN
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, 20814, USA.
Hoffman
R W
RW
Tsokos
G C
GC
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001324:Autoantigens / Q000097:blood / Q000276:immunology; D017252:CD3 Complex / Q000502:physiology*; D002118:Calcium / Q000097:blood; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000276:immunology / Q000378:metabolism; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D017411:Ribonucleoproteins, Small Nuclear / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D014443:Tyrosine / Q000378:metabolism
D000911:Antibodies, Monoclonal; D001324:Autoantigens; D017252:CD3 Complex; D011506:Proteins; D011948:Receptors, Antigen, T-Cell; D017411:Ribonucleoproteins, Small Nuclear; D014443:Tyrosine; D002118:Calcium