Journal
FRONTIERS IN IMMUNOLOGY
Volume 6, Issue -, Pages 1-18Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2015.00582
Keywords
melanoma; immunotherapy; cytotoxic T cells; TCR affinity; TCR structural avidity; tumor antigens; T cell functionality; NTAmers
Categories
Funding
- Department of Oncology
- University of Lausanne
- ISREC Foundation
- Canadian Institute of Health Research
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Cytotoxic T cells recognize, via their T cell receptors (TeRs), small antigenic peptides presented by the major histocompatibility complex (pMHC) on the surface of professional antigen-presenting cells and infected or malignant cells. The efficiency of T cell triggering critically depends on TCR binding to cognate pMHC, i.e., the TCR-pMHC structural avidity. The binding and kinetic attributes of this interaction are key parameters for protective T cell-mediated immunity, with stronger TCR-pMHC interactions conferring superior T cell activation and responsiveness than weaker ones. However, high avidity TCRs are not always available, particularly among self/tumor antigen-specific T cells, most of which are eliminated by central and peripheral deletion mechanisms. Consequently, systematic assessment of T cell avidity can greatly help distinguishing protective from non-protective T cells. Here, we review novel strategies to assess TCR-pMHC interaction kinetics, enabling the identification of the functionally most-relevant T cells. We also discuss the significance of these technologies in determining which cells within a naturally occurring polyclonal tumor specific T cell response would offer the best clinical benefit for use in adoptive therapies, with or without T cell engineering.
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