CD8 co-receptor enhances T cell activation without any effect on initial attachment

Abstract

The scanning of surrounding tissues by T lymphocytes to detect cognate antigen is a highly demanding process that requires high rapidity, sensitivity and specificity. Co-receptors such as CD8 are known to increase detection performance, but the exact mechanism of this role remains incompletely understood. Here, we used interference reflection microscopy to image the initial spreading of 1G4 receptor transfected CD8+ and CD8- Jurkat cells dropped on surfaces exposing five cognate antigens of varying activating power, and we used a laminar flow chamber to measure the influence of CD8 on the kinetics of bond formation and rupture between cell-born T cell receptors (TCRs) and peptide-exposing major histocompatibility complex antigens (pMHCs) at the single molecule level. It is concluded that CD8 did not influence TCR-pMHC interaction during the first seconds following cell surface encounter, but it promoted the spreading responses during the first minutes, thus suggesting that CD8 was involved in early activation rather than binding. In addition, presented results were quantitatively compared with a recent report on the cell-free interaction between the same ligand-receptor couples : it is concluded that bond formation was strongly impaired by cell molecular environment, while bond rupture was comparable in both systems. Results from this and previous reports were used to propose a quantitative scheme of the strategy used by T lymphocytes to scan foreign surfaces. It is suggested that the understanding of the strategy used by cells to perform their basic functions may be a prerequisite to understand the function of molecular networks revealed by high throughput methods.