The Molecular Genetics of the T-Cell Antigen Receptor and T-Cell Antigen Recognition

Abstract

The genes encoding the alpha and beta chain of the T-cell receptor and the gamma gene have been cloned, and their structure, organization, ontogeny of expression, pattern of rearrangement, and diversification are now generally understood. In most cases, the immunoglobulin paradigm applied very well to the corresponding phenomena in T cells, although as described above, some interesting and potentially important differences exist. Nevertheless, there are still many unanswered questions regarding the ontogeny and mechanism of MHC-restricted antigen recognition, and it is not clear how far the immunoglobulin model can take us in understanding these phenomena. Although the alpha/beta heterodimer looks like an antibody and the binding sites of the two molecules may be similar, the rules governing B- and T-cell activation are clearly different, and the ligand(s) bound by the receptor are still poorly characterized. In the future, T-cell receptor genes, as well as those encoding the T-cell accessory molecules, will be altered in vitro and transferred into mammalian cells in culture and into whole organisms in an attempt to understand T-cell antigen recognition. These tools will allow us to manipulate the mammalian immune response in a variety of different ways that will have a profound impact both on our understanding of immunology and on medicine in the future.