Fc epsilon receptor type I gamma chain replaces the deficient T cell receptor zeta chain in T cells of patients with systemic lupus erythematosus

Arthritis Rheum. 2001 May;44(5):1114-21. doi: 10.1002/1529-0131(200105)44:5<1114::AID-ANR192>3.0.CO;2-B.


Objective: T cells from the majority of patients with systemic lupus erythematosus (SLE) express significantly lower levels of T cell receptor zeta chain, a critical signaling molecule. However, TCR/CD3 triggering of SLE T cells shows increased phosphorylation of downstream signaling intermediates and increased [Ca2+]i response, suggesting the presence of alternative signaling mechanisms. We investigated whether Fcepsilon receptor type I gamma chain (FcepsilonRIgamma) could substitute for TCR zeta chain and contribute to T cell signaling in SLE.

Methods: T cells were purified from the peripheral blood of 21 patients with SLE and 5 healthy volunteers. The expression of FcepsilonRIgamma was investigated using immunoblotting, reverse transcriptase-polymerase chain reaction, and flow cytometry methods. Involvement of the FcepsilonRIgamma in T cell signaling was studied by immunoprecipitation and/or immunoblotting after TCR/CD3 stimulation.

Results: Western blotting and densitometric analysis showed that the expression of FcepsilonRIgamma in SLE T cells was 4.3-fold higher than in normal T cells (P < 0.001). Flow cytometric analyses of T lymphocyte subsets revealed that the proportions of FcepsilonRIgamma+,CD3+, FcepsilonRIgamma+,CD4+, and FcepsilonRIgamma+, CD8+ cells were significantly greater in SLE patients than in healthy controls (P < 0.001). Immunoprecipitation of SLE T cell lysates with an anti-FcepsilonRIgamma antibody showed that FcepsilonRIgamma associates with the tyrosine kinase Syk and the CD3epsilon chain, suggesting that FcepsilonRIgamma is functionally involved in TCR signaling.

Conclusion: These results demonstrate that the FcepsilonRIgamma chain is expressed at high levels in a large proportion of SLE T cells. The increased expression of FcepsilonRIgamma chain in SLE T cells may account in part for the aberrant antigen receptor-initiated signaling and contribute to the diverse cellular abnormalities found in this disease.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies / pharmacology
  • CD3 Complex / immunology
  • CD3 Complex / metabolism*
  • CD4-Positive T-Lymphocytes / enzymology
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / enzymology
  • CD8-Positive T-Lymphocytes / immunology
  • Enzyme Precursors / metabolism
  • Female
  • Gene Expression / immunology
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Lupus Erythematosus, Systemic / immunology*
  • Lupus Erythematosus, Systemic / metabolism*
  • Male
  • Middle Aged
  • Phosphorylation
  • Protein-Tyrosine Kinases / metabolism
  • RNA, Messenger / analysis
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / metabolism*
  • Receptors, IgE / genetics
  • Receptors, IgE / immunology
  • Receptors, IgE / metabolism*
  • Signal Transduction / immunology
  • Syk Kinase


  • Antibodies
  • CD3 Complex
  • CD3 antigen, zeta chain
  • Enzyme Precursors
  • Intracellular Signaling Peptides and Proteins
  • RNA, Messenger
  • Receptors, Antigen, T-Cell
  • Receptors, IgE
  • Protein-Tyrosine Kinases
  • SYK protein, human
  • Syk Kinase