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Author Notes:

Email Address:Brian D. Evavold : bevavol@emory.edu

The authors would like to thank Rakieb Andargachew, Dennis Neeld, Lori Blanchfield and Anna Kersh for helpful discussion

The authors would like to thank Rakieb Andargachew, Dennis Neeld, Lori Blanchfield and Anna Kersh for helpful discussion.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Research Funding:

This work was supported by NIH grant T32 AI007610, RO1 NS071518, and RO1 AI110113 to BE and F31 NS086130 to RM.


  • TCR affinity
  • 2D assays
  • tetramers
  • T cells
  • T cell diversity

Lower Affinity T Cells are Critical Components and Active Participants of the Immune Response


Journal Title:

Frontiers in Immunology


Volume 6


Type of Work:

Article | Final Publisher PDF


Kinetic and biophysical parameters of T cell receptor (TCR) and peptide:MHC (pMHC) interaction define intrinsic factors required for T cell activation and differentiation. Although receptor ligand kinetics are somewhat cumbersome to assess experimentally, TCR:pMHC affinity has been shown to predict peripheral T cell functionality and potential for forming memory. Multimeric forms of pMHC monomers have often been used to provide an indirect readout of higher affinity T cells due to their availability and ease of use while allowing simultaneous definition of other functional and phenotypic characteristics. However, multimeric pMHC reagents have introduced a bias that underestimates the lower affinity components contained in the highly diverse TCR repertoires of all polyclonal T cell responses. Advances in the identification of lower affinity cells have led to the examination of these cells and their contribution to the immune response. In this review, we discuss the identification of high- vs. low-affinity T cells as well as their attributed signaling and functional differences. Lastly, mechanisms are discussed that maintain a diverse range of low- and high-affinity T cells.

Copyright information:

© 2015 Martinez and Evavold.

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