The T cell antigen receptor: "The Hunting of the Snark"

Abstract

The quest to clone the genes encoding the T cell antigen receptor (TCR) was a tale akin to Lewis Carroll's "The Hunting of the Snark". After a long and often frustrating search, back-to-back papers reporting the discovery of the genes encoding the mouse and human TCR were finally published in the March 8, 1984 edition of Nature. In this account, I outline how my laboratory hunted the human form of the Snark, and what our discovery meant to both the immunology community and me personally. Since the isolation of the TCR genes 23 years ago, more than 30,000 papers have been published on subjects as varied as central tolerance, peripheral tolerance, TCR crystal structure, and how TCR bind to peptide/MHC structures. Numerous clinical studies involving aspects of TCR biology have also been reported. Here, I briefly discuss how the knowledge generated from our discovery has been applied to basic and clinical immunology, and where it might take us in the future.