Building a multichain receptor: synthesis, degradation, and assembly of the T-cell antigen receptor

Abstract

The murine T-cell antigen receptor consists of at least seven chains and six different proteins. The two clonotypic chains alpha and beta are glycoproteins of 40-45 kDa present as a disulfide-linked heterodimer. Four clonally invariant chains include delta (a 26-kDa glycoprotein), gamma (a 21-kDa glycoprotein), epsilon (a 25-kDa protein), and zeta (a 16-kDa protein). zeta is found in the complex as a disulfide-linked homodimer. The clonotypic chains and the invariant chains form a noncovalent complex on the cell surface. We have developed antibodies against each of the chains and used them to examine the assembly of the mature complex in the murine antigen-specific T-cell hybridoma 2B4. Pulse-chase studies of metabolically labeled cells demonstrate that many of the chains are synthesized in great excess over the amount assembled into the mature complex. These excess chains, either as free components or as partially assembled complexes, are rapidly degraded. This degradation most likely takes place in the lysosomes. The complete complex is quite stable with a long half-life. A specific hierarchy of partially assembled complexes can be discerned.