Stoichiometry and intracellular fate of TRIM-containing TCR complexes

Mahima Swamy, Gabrielle M. Siegers, Gina J. Fiala, Eszter Molnar, Elaine P. Dopfer, Paul Fisch, Burkhart Schraven, Wolfgang W.A. Schamel (Lead / Corresponding author)

Research output: Contribution to journalReview articlepeer-review

10 Citations (Scopus)
62 Downloads (Pure)


Background: Studying the stoichiometry and intracellular trafficking of the T cell antigen receptor (TCR) is pivotal in understanding its mechanisms of activation. The αβTCR includes the antigen-binding TCRαβ heterodimer as well as the signal transducing CD3εγ, CD3εδ and ζ2subunits. Although the TCR-interacting molecule (TRIM) is also part of the αβTCR complex, it has not been included in most reports so far. Results: We used the native antibody-based mobility shift (NAMOS) assay in a first dimension (1D) blue native (BN)-PAGE and a 2D BN-/BN-PAGE to demonstrate that the stoichiometry of the digitonin-solublized TRIM-containing αβTCR is TCRαβCD3ε2γ δζ2TRIM2. Smaller αβTCR complexes possess a TCRαβ CD3ε2γδζ 2stoichiometry. Complexes of these sizes were detected in T cell lines as well as in primary human and mouse T cells. Stimulating the αβTCR with anti-CD3 antibodies, we demonstrate by confocal laser scanning microscopy that CD3ε colocalizes with ζ and both are degraded upon prolonged stimulation, possibly within the lysosomal compartment. In contrast, a substantial fraction of TRIM does not colocalize with ζ. Furthermore, TRIM neither moves to lysosomes nor is degraded. Immunoprecipitation studies and BN-PAGE indicate that TRIM also associates with the γδTCR. Conclusions: Small αβTCR complexes have a TCRαβ CD3ε2γδζ 2stoichiometry; whereas those associated with one TRIM dimer are TCRαβ CD3ε2γδζ2TRIM 2. TRIM is differentially processed compared to CD3 and ζ subunits after T cell activation and is not degraded. The γδTCR also associates with TRIM.

Original languageEnglish
Article number5
Pages (from-to)1-10
Number of pages10
JournalCell Communication and Signaling
Publication statusPublished - 18 Mar 2010

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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