Siglec Expression on T Cells

CD33-related Siglecs are  signaling molecules that are expressed on most immune cells, and are mostly thought to downregulate cellular activation via cytosolic immunoreceptor tyrosine-based inhibitory motifs. Human T lymphocytes are a striking exception, expressing little to none of these receeptors. In striking contrast, T lymphocytes from “great apes” express several CD33-related Siglecs on their surfaces. This human-specific loss of T cell Siglec expression thus seems to have occurred after our last common ancestor with great apes, potentially causing a loss of inhibitory signaling. In keeping with this proposed "loss of brakes", human T cells give much stronger proliferative responses to specific activation via antibodies against the T cell receptor complex (a mimic of physiological activation), compared to those from chimpanzees. This human-specific loss of T cell CD33-related Siglec expression is associated with T cell hyperactivity, and may help explain the  apparently disparate prevalence and severity of T cell-mediated diseases between humans and chimpanzees