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Analysis of peptide/MHC-induced TCR downregulation

Deciphering the triggering kinetics

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Abstract

The interaction of T0lymphocytes with antigen-presenting cells displaying a small number of specific peptide/major histocompatibility complexes results in the downregulation of a large number of T-cell receptors (TCR), suggesting serial TCR triggering. However, the details of TCR downregulation are controversial. In particular, the level of comodulation of nonengaged TCR reported by different authors ranges from essentially none to considerable levels. Here, we address this controversy using complementary experimental and mathematical techniques. We find that TCR downregulation is very rapid during the first 2–4 min after T-cell antigen-presenting cells contact formation. After this phase, TCR downregulation proceeds at a relatively slow rate. Statistical and computational analyses show that this pronounced change in downregulation kinetics is compatible with the notion of initial serial triggering of clustered TCR followed by serial triggering of individual TCR. We further propose a compatible mechanism for concurrent triggering of multiple TCR by a single peptide/major histocompatibility complex. We provide a unified picture of productive TCR engagement and downregulation in which TCR triggering characteristics evolve from an initial cooperative phase to a sustained phase of signal accumulation.

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Authors and Affiliations

  1. INSERM U563, Institut Claude de Preval, CHU Purpan, 31059, Toulouse Cedex 3, France

    Clemens Utzny, Sabina Müller & Salvatore Valitutti

  2. Department of Mathematics, University of British Columbia, 1984 Mathematics Road, V6T 1Z2, British Columbia, Vancouver, Canada

    Daniel Coombs

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  1. Clemens Utzny
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  2. Daniel Coombs
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  3. Sabina Müller
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  4. Salvatore Valitutti
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Correspondence to Daniel Coombs.

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Utzny, C., Coombs, D., Müller, S. et al. Analysis of peptide/MHC-induced TCR downregulation. Cell Biochem Biophys 46, 101–111 (2006). https://doi.org/10.1385/CBB:46:2:101

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