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Evidence for multivalent structure of T-cell antigen receptor complex
M Exley1, T Wileman, B Mueller
1Division of Immunology, Beth Israel Hospital, Harvard Medical School, Boston, MA 02215, USA.
Molecular Immunology
|August 1, 1995
Summary
The T-cell receptor (TCR) complex, crucial for T-cell immunity, may contain multiple alpha beta heterodimers. This suggests a larger, potentially divalent structure for the TCR-CD3 complex, impacting T-cell antigen recognition.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- The T-cell receptor (TCR) complex, composed of alpha beta or gamma delta TCR chains and CD3 polypeptides (gamma, delta, epsilon, zeta), is essential for adaptive immunity.
- The precise molecular mass and stoichiometry of the TCR-CD3 complex remain uncertain, hindering a full understanding of its structure and function.
Purpose of the Study:
- To investigate the molecular composition and stoichiometry of the T-cell receptor (TCR)-CD3 complex.
- To determine if TCR complexes can contain more than one alpha beta heterodimer.
Main Methods:
- Analysis of T-T hybridoma cells expressing distinct TCR heterodimers.
- Co-modulation assays using specific monoclonal antibodies (mAbs) to track TCR surface expression.
- Density gradient sedimentation analysis to determine the molecular size and complex formation of TCR.
Main Results:
- Co-modulation of two distinct V alpha V beta heterodimers suggested the presence of multiple alpha beta heterodimers within a single TCR complex.
- Density gradient sedimentation revealed that cell surface TCR complexes exhibit sedimentation coefficients (18 +/- 3S) significantly larger than predicted for a monovalent structure, indicating higher-order complexes.
- TCR complexes sedimented as large structures (approx. 443 kDa), contrasting with the smaller IgM B-cell receptor (approx. 300 kDa).
Conclusions:
- T-cell antigen receptors can incorporate more than one alpha beta heterodimer.
- The findings support a model of a larger, potentially divalent TCR-CD3 complex (e.g., 10-chain structure), challenging previous assumptions about TCR stoichiometry.