Cdc42 defect reveals the role of microvilli in antigen recognition and chemokinesis during T cell development

Abstract

Microvilli on the surface of T cells differ from those on epithelial cells as they exhibit filopodia-like characteristics that aid in the structural support for clustering molecules essential for sensing and cell migration. However, little is known how microvilli are organized during T-cell developments. Electron microscopy revealed that single-positive thymocytes have more and longer microvilli than double-positive thymocytes. Intriguingly, knocking out Cdc42, a small Rho family protein, significantly reduced the number and length of microvilli in single-positive thymocytes, leading to reduced cell mass and downregulation of surface receptors TCR, CCR7, and LFA-1. These effects resulted in decreased T-cell adhesion to high-endothelial venules and weakened antigen recognition capability for T-cell activation, while not affecting intrinsic migratory traits. This discovery offers the initial evidence that Cdc42 plays a pivotal role in assembling surface microvilli during T-cell development, ultimately contributing to the proper maturation and functionality of T-cells.