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T cell affinity regulates asymmetric division, effector cell differentiation, and tissue pathology
Carolyn G King1, Sabrina Koehli, Barbara Hausmann
1Laboratory of Transplantation Immunology, Department of Biomedicine, University Hospital Basel and University of Basel, Switzerland. carolyn.king@unibas.ch
Immunity
|October 23, 2012
Summary
T cell receptor (TCR) interaction strength dictates T cell responses. High-affinity TCR binding triggers asymmetric T cell division, promoting effector cell differentiation and tissue-specific immune responses.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- T cell receptor (TCR) affinity for peptide-major histocompatibility complex (pMHC) is critical for T cell activation.
- The link between TCR signal strength and T cell differentiation into effector cells remains incompletely understood.
Purpose of the Study:
- To investigate the role of asymmetric T cell division in linking TCR signal strength to effector T cell differentiation.
- To determine how antigen affinity influences T cell division patterns and subsequent immune responses.
Main Methods:
- Studied T cell activation using varying pMHC affinities.
- Analyzed T cell division patterns (symmetric vs. asymmetric).
- Assessed effector cell differentiation markers, including VLA-4 integrin expression and tissue infiltration capacity.
Main Results:
- Recognition of pMHC above a threshold affinity induced asymmetric T cell division.
- Asymmetric division resulted in proximal daughter cells that extensively divided and differentiated into short-lived effector cells expressing VLA-4.
- These effector cells infiltrated peripheral tissues and mediated target destruction.
- Below-threshold antigen recognition led to symmetric division, abortive expansion, and impaired effector differentiation.
Conclusions:
- Antigen affinity and asymmetric T cell division are key regulators of CD8(+) T cell fate specification.
- Asymmetric division serves as a mechanistic link between high TCR signal strength and the development of tissue-infiltrating effector T cells.
- These findings predict the potential of self-reactive T cells to cause tissue pathology.
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