The T cell receptor gene and its association with human diseases

The genetic organization and protein structure of the T cell receptor (TCR)/CD3 complex are currently under investigation, and recent work has provided information about its assembly, expression and function. This article reviews what is currently known about the structure and assembly of the TCR/CD3 complex. The TCR chains are members of the immunoglobulin gene superfamily and are generated by combinatorial associations of V, J, D, and C genes. The presence of certain gene rearrangements within these chains has been associated with lymphoproliferative disorders, autoimmune disease and immunodeficiencies. TCR rearrangements can be useful in the diagnosis of lymphoproliferative disorders and in the identification of patients who will subsequently relapse, once in remission. With respect to autoimmune disease, the possibility now exists of immunotherapy with TCR designer polypeptides to prevent disease. In patients with primary immunodeficiencies secondary to defects in expression of the TCR, the possibility of somatic gene therapy now exists. As more information unfolds about the role that TCR gene rearrangements have in various diseases, new insights are gained into better diagnosis and treatment.