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Functional avidity maturation of CD8+ T cells without selection of higher affinity TCR

Nature Immunology volume 2, pages 711–717 (2001)Cite this article

Abstract

Unlike B cells, T cells lack the capacity to improve the affinity of their antigen receptors by somatic mutation. It is, therefore, believed that optimization of cellular immunity is mediated almost exclusively through selective expansion of T cells bearing receptors with the highest affinity for antigen. We show here that T cell responsiveness to peptide (termed “functional avidity”) increased>50-fold during the early stages of viral infection. This indicated that T cells, like B cells, undergo extensive functional maturation in vivo. However, in contrast to B cells, maturation of the T cell response can occur without any appreciable change in T cell receptor affinity.

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Figure 1: Functional avidity maturation of an antigen-specific T cell response.
Figure 2: Anti-CD8 preferentially blocks peptide-specific activation of low-avidity T cells.
Figure 3: Characterization of TCRs on antigen-specific T cells of low or high functional avidity.
Figure 4: Functional avidity maturation in the absence of clonal selection.
Figure 5: Functional avidity does not correlate with the expression of activation and adhesion molecules.
Figure 6: Lck expression is increased in antigen-specific LFA-1hiCD8+ T cells.
Figure 7: Correlation between higher Lck expression and increased IFN-γ production in antigen-specific T cells.

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Acknowledgements

We thank A. Lord for secretarial support, R. Pagarigan for technical assistance and C. T. Nugent, R. Soloff and D. Parker for helpful discussions. NP(118–126) and GP(33–41) tetramers were prepared by the NIH Tetramer Core Facility in Atlanta, GA. Supported by NIH grant AI-27028.

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  1. Mark K. Slifka

    Present address: OHSU Vaccine and Gene Therapy Institute, Beaverton, OR, 97006, USA

Authors and Affiliations

  1. Department of Neuropharmacology, The Scripps Research Institute, La Jolla, 92037, CA, USA

    Mark K. Slifka & J. Lindsay Whitton

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Correspondence to Mark K. Slifka.

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Slifka, M., Whitton, J. Functional avidity maturation of CD8+ T cells without selection of higher affinity TCR. Nat Immunol 2, 711–717 (2001). https://doi.org/10.1038/90650

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