CD6

CD6 is a cell-surface glycoprotein that belongs to the CD2 family of the immunoglobulin superfamily. It is a single-pass type I membrane protein characterized by three extracellular scavenger receptor cysteine-rich (SRCR) domains and a cytoplasmic tail capable of signaling. In humans, CD6 is primarily expressed on T cells and thymocytes, with detectable expression on a subset of natural killer cells.

The main extracellular ligand of CD6 is ALCAM (CD166). The CD6-ALCAM interaction promotes cell adhesion and contributes to the formation of the immunological synapse between T cells and antigen-presenting cells, supporting receptor–ligand engagement that can influence T cell responses.

Functionally, CD6 participates in T cell activation and modulation of T cell receptor signaling, influences thymocyte development, and can impact T cell migration to sites of inflammation. By shaping costimulatory signals and adhesion, CD6 helps regulate the magnitude and character of T cell responses.

Clinically, CD6 is pursued as a therapeutic target in autoimmune and inflammatory diseases. Anti-CD6 antibodies, such as itolizumab, have been developed and approved in some regions for psoriasis and are studied for other conditions, including rheumatoid arthritis and multiple sclerosis, with the aim of dampening pathogenic T cell activity through disruption of the CD6-ALCAM axis. The CD6 pathway remains an active area of basic and translational research.