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. 2012 Aug 28:3:272.
doi: 10.3389/fimmu.2012.00272. eCollection 2012.

The Serial Engagement Model 17 Years After: From TCR Triggering to Immunotherapy

Salvatore Valitutti  1
Affiliations

The Serial Engagement Model 17 Years After: From TCR Triggering to Immunotherapy

Salvatore Valitutti. Front Immunol. .

Abstract

More than 15 years ago the serial engagement model was proposed as an attempt to solve the low affinity/high sensitivity paradox of TCR antigen recognition. Since then, the model has undergone ups and downs marked by the technical and conceptual advancements made in the field of T lymphocyte activation. Here, I describe the development of the model and survey recent literature providing evidence either for or against the idea that serial TCR/pMHC engagement might contribute to T lymphocyte activation. I also discuss how the concept of serial TCR engagement might be useful in the design of immunotherapeutic approaches aimed at potentiating T lymphocyte responses in vivo.

Keywords: T cell antigen receptor; T lymphocyte activation; TCR serial engagement; immunological synapse; signal transduction.

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Figures

Figure 1
Figure 1
The serial TCR engagement model. At the IS, a few specific pMHC (red) sequentially trigger incoming TCR resulting in sustained signaling. Triggered TCR are internalized and targeted to lysosomes for degradation while unbound pMHC bind new TCR.
Figure 2
Figure 2
(A) The serial engagement model postulates that pMHC ligands exhibiting optimal binding half-lives to TCR behave as optimal agonists; (B) At high pMHC densities, pMHC exhibiting long binding half-lives are stimulatory; (C) At low pMHC densities, pMHC exhibiting long binding half-lives fail to trigger T cell responses.
See this image and copyright information in PMC

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