Selection of Amino Acid Sequences in the Beta Chain of the T Cell Antigen Receptor

TLDR

The immune response in mammals is initiated by T lymphocytes whose antigen receptors contain highly variable regions that mediate specificity through simultaneous recognition of foreign antigens and MHC molecules, a mechanism distinct from immunoglobulins. The authors investigated the relationship between receptor structure and specificity by analyzing primary sequences of the β‑chain from T lymphocyte clones specific for pigeon cytochrome c. They found a striking selection for specific amino acid sequences in the β‑chain’s CDR3‑like region, indicating that analogous variable regions are crucial for ligand specificity in T cell receptors.

Abstract

The induction of an immune response in mammals is initiated by specifically reactive T lymphocytes. The specificity of the reaction is mediated by a complex receptor, part of which is highly variable in sequence and analogous to immunoglobulin heavy- and light-chain variable domains. The functional specificity of the T cell antigen receptor is, however, markedly different from immunoglobulins in that it mediates cell-cell interactions via the simultaneous recognition of foreign antigens and major histocompatibility complex-encoded molecules expressed on the surface of various lymphoid and nonlymphoid cells. The relation between the structure of the receptor and its functional specificity was investigated by analyzing the primary sequences of the receptors expressed by a series of T lymphocyte clones specific for a model antigen, pigeon cytochrome c. Within this set of T lymphocyte clones there was a striking selection for amino acid sequences in the receptor β-chain in the region analogous to the third complementarity-determining region of immunoglobulins. Thus, despite the functional differences between T cell antigen receptors and immunoglobulin molecules, analogous regions appear to be important in determining ligand specificity.