CD8 Co-Receptor Enhances T-Cell Activation without Any Effect on Initial Attachment.

Philippe Robert,Pierre Bongrand,P Anton Van Der Merwe,Laurent Limozin

doi:10.3390/cells10020429

Abstract

The scanning of surrounding tissues by T lymphocytes to detect cognate antigens requires high speed, sensitivity and specificity. T-cell receptor (TCR) co-receptors such as CD8 increase detection performance, but the exact mechanism remains incompletely understood. Here, we used a laminar flow chamber to measure at the single molecule level the kinetics of bond formation and rupture between TCR- transfected CD8+ and CD8− Jurkat cells and surfaces coated with five peptide-exposing major histocompatibility antigens (pMHCs) of varying activating power. We also used interference reflection microscopy to image the spreading of these cells dropped on pMHC-exposing surfaces. CD8 did not influence the TCR–pMHC interaction during the first few seconds following cell surface encounter, but it promoted the subsequent spreading responses, suggesting that CD8 was involved in early activation rather than binding. Further, the rate and extent of spreading, but not the lag between contact and spreading initiation, depended on the pMHC. Elucidating T-lymphocyte detection strategy may help unravel underlying signaling networks.

Highlights

The detection by T lymphocytes of foreign peptides (p) bound to major histocompatibility complex (MHC)-encoded proteins is a key and early step of immune responses
We have previously shown that the maximum spreading rate determined during the first 3 min after contact was robustly correlated to peptideexposing major histocompatibility antigens (pMHCs) activation potency [27]
CD8 Did Not Increase the Rate of Cell Attachment to pMHC-Coated Surfaces

Summary

Introduction

The detection by T lymphocytes of foreign peptides (p) bound to major histocompatibility complex (MHC)-encoded proteins (pMHC) is a key and early step of immune responses. This initial event can generate a wide range of cellular outcomes, including expression of activation antigens such as CD69, production of mediators such as IL-2, triggering of differentiation or proliferation programs, rapid destruction of a target cell, or even T-cell inactivation. It would be of obvious theoretical and practical interest to gain an accurate understanding of the links between molecular events involved in this process. While an impressive amount of information has been obtained in the last few years, our understanding of the activation process remains incomplete and some key information is lacking

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