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Tailoring In Vivo Cytotoxicity Assays to Study Immunodominance in Tumor-specific CD8+ T Cell Responses
Published on: May 6, 2019
Relationship between CD8-dependent antigen recognition, T cell functional avidity, and tumor cell recognition.
Tamson V Moore1, Gretchen E Lyons, Natasha Brasic
1Department of Surgery, The University of Chicago, Chicago, IL 60637, USA.
Understanding T cell receptor (TCR) affinity is key for effective immunotherapy. This study shows that T cell functional avidity can be modulated independently of TCR affinity, impacting immunotherapy strategies.
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Area of Science:
- Immunology
- Cancer Immunotherapy
- Molecular Biology
Background:
- Effective T cell receptor (TCR) gene-modified T cell immunotherapy relies on understanding TCR affinity and T cell functional avidity.
- High functional avidity T cells are crucial for successful cancer immunotherapy.
Purpose of the Study:
- To evaluate the relative affinity of two TCRs from high functional avidity T cell clones.
- To investigate the relationship between TCR affinity, functional avidity, and CD8 independence in T cell recognition.
Main Methods:
- Isolated and characterized two TCRs from HLA-A2-restricted, gp100-reactive T cell clones.
- Expressed these TCRs in CD8- Jurkat cells for functional avidity and antigen recognition assays.
- Assessed recognition of peptide-loaded T2 cells and HLA-A2+ melanoma cells.
Main Results:
- TCRs from high functional avidity clones were evaluated.
- Jurkat cells expressing these TCRs showed high functional avidity but failed to recognize melanoma cells.
- CD8-independent recognition by the original clone did not transfer to Jurkat cells.
Conclusions:
- T cell functional avidity does not directly correlate with TCR affinity.
- CD8 independence in antigen recognition is not always transferable via TCR expression.
- T cells possess mechanisms to modulate functional avidity independently of TCR affinity, impacting immunotherapy design.