Activated TCRs remain marked for internalization after dissociation from pMHC

  • A Corrigendum to this article was published on 01 November 2002


To assess the roles of serial engagement and kinetic proofreading in T cell receptor (TCR) internalization, we have developed a mathematical model of this process. Our determination of TCR down-regulation for an array of TCR mutants, interpreted in the context of the model, has provided new information about peptide-induced TCR internalization. The amount of TCR down-regulation increases to a maximum value and then declines as a function of the half-life of the bond between the TCR and peptide–major histocompatibility complex (pMHC). The model shows that this behavior, which reflects competition between serial engagement and kinetic proofreading, arises only if it is postulated that activated TCRs remain marked for internalization after dissociation from pMHC. The model also predicts that because of kinetic proofreading, the range of TCR-pMHC–binding half-lives required for T cell activation depends on the concentrations and localization of intracellular signaling molecules. We show here that kinetic proofreading provides an explanation for the different requirements for activation observed in naïve and memory T cells.

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Figure 1: Model geometry.
Figure 2: The monomer model for TCR internalization.
Figure 3: TCR internalization as a function of the dissociation rate constant.
Figure 4: TCR down-regulation as a function of TCR-pMHC half-life.
Figure 5: Relation between peak TCR internalization and the lifetime of the unbound activated state.
Figure 6: Effect of increasing the rate constant for biochemical modification.

Change history

  • 09 October 2002

    print was mistakenly not corrected for october issue, so a revision to the note was made to indicate that nov. issue would contain a printed corrigendum; pdf was also appended with corrigendum that will appear in the nov. issue

  • 12 September 2002

    All instances of Fig. 4 were updated with note and PDF was appended with note. Issue PDF will contain "corrected 12 September 2002 (details online)"


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Supported by National Institutes of Health grant GM35556 and National Science Foundation grant MCB9723897 and performed, in part, under the auspices of the U.S. Department of Energy. A. M. K. is supported by the Helen Hay Whitney Foundation.

*Note: In the AOP version of this article, the second sentence of the legend to Fig. 4 contained an error. This sentence should read: "Each point represents the indicated TCR-pMHC pair: 1, V98D- Kb-VSV; 2, V98L-Kb-VSV; 3, N30.7-KbA158T-VSV; 4, G99A-KbA158T-VSV; 5, G97/99A-KbA158T-VSV; 6, G97A-KbA158T-VSV; 7, N30.7- Kb-VSV; 8, G97A-Kb-VSV; 9, G97/99A- Kb-VSV; 10, G99A-Kb-VSV." This error has been corrected in the HTML version but appears incorrectly in print. A printed corrigendum will appear in the November 2002 issue of Nature Immunology, when the PDF version available online will also be appended.

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Correspondence to Byron Goldstein.

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Coombs, D., Kalergis, A., Nathenson, S. et al. Activated TCRs remain marked for internalization after dissociation from pMHC. Nat Immunol 3, 926–931 (2002).

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