Research ArticleImmunology

TCR-Ligand koff Rate Correlates with the Protective Capacity of Antigen-Specific CD8+ T Cells for Adoptive Transfer

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Science Translational Medicine  03 Jul 2013:
Vol. 5, Issue 192, pp. 192ra87
DOI: 10.1126/scitranslmed.3005958

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Knocking Off T Cell Avidity

Adoptive cell transfer is a burgeoning therapeutic approach being used for everything from cancer immunotherapy to treating chronic infections. However, selecting the most effective T cells for a given antigen has remained a challenge. T cell receptors (TCRs) with higher avidity for their cognate ligands recognize their targets earlier and faster than lower-avidity TCRs, but rapid screening of TCR avidity has been difficult. Now, Nauerth et al. use real-time microscopy to measure the dissociation of monomeric peptide-MHC molecules and determine that these measures can be correlated with efficacy of adoptive immunotherapy.

The authors use Streptamer-based assay to determine avidity on living T cells. They found a surprising diversity of avidity in cytomegalovirus (CMV)–specific T cells derived from different individuals. What’s more, their measure of avidity (koff rate) correlated with in vivo protectivity of T cells in animal models of CMV and Listeria monocytogenes infection. These data suggest that this method may help not only to determine which cells are most suitable for adoptive transfer but also to measure the quality of an endogenous immune response.

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