Maturation of cytotoxic T lymphocytes is mediated in part by a structure on the T cell surface known as the T cell antigen receptor (TCR) complex. The pre-TCR complex consists of pre-TCR α, pre-TCR βand CD3, which together help coordinate early thymocyte development. Pre-TCR α chain is a type I transmembrane glycoprotein with an extracellular region similar to the constant domain of the immunoglobulin supergene family. Notch3 transgenic mice lacking pre-TCR α inhibits tumor development. In humans, acute lymphoblastic leukemias (ALL) in remission have lower transcript levels of Notch3, HES-1 and pre-TCR α transcripts a and b relative to proliferating ALLs. The human pre-TCR α gene is expressed in immature T cells and maps to chromosome 6p21.3.