Optimal T cell activation requires the engagement of CD6 and CD166

The T cell surface glycoprotein, CD6 binds CD166 in the first example of an interaction between a scavenger receptor cysteine-rich domain and an immunoglobulin-like domain. We report that in human these proteins interact with a K-D =0.4-1.0 muM and K-off greater than or equal to 0.4-0.63 s(-1), typical of many leukocyte membrane protein interactions. CD166 also interacts in a homophilic manner but with around 100-fold lower affinity (K-D = 29-48 muM and K-off greater than or equal to 5.3 s(-1)). At concentrations, that will block the CD6/CD166 interaction, soluble monomeric CD6 and CD166 inhibit antigen-specific human T cell responses. This is consistent with extracellular engagement between CD6 and CD166 being required for an optimal immune response.