Antigen-specific, major histocompatibility complex-restricted T cell receptors

Abstract

In this paper we have summarized our work on the structure of the receptor for Ag/MHC on 3 T cell hybridomas. In each case, these receptors have been identified by their reaction with antibodies, thought to be directed against Ag/MHC receptors because of their clone-specificity, and their ability to interfere with Ag/MHC recognition by the relevant hybridoma. The antibodies precipitate approximately 85 kd molecular weight heterodimeric glycoproteins from these cells. These reduce to 2 chains of 40-43 kd, one of acidic and the other of basic pI. These bulk characteristics apply to receptors from Class II-restricted, as well as Class I-specific T cells. There is evidence of molecular weight heterogeneity for both alpha and beta-chains in the mouse, both having 40 and 43 kd forms. Isoelectric focussing patterns suggest that both chains vary in amino acid sequence between clones. Peptide maps show that the receptor varies in amino acid sequence between clones, but that some peptides appear common, i.e., the receptor seems to have both variable and constant amino acid sequences. It is even possible that allotypic differences between the peptide maps of BALB/c and C57BL/6-derived receptors have been identified, though more data will be needed to confirm this. Finally we have recently shown that reaction with an anti-idiotype predicts both the Ag and MHC specificity of the T cell hybridoma bearing it, suggesting that a single receptor, responsible for binding both Ag and MHC, is identified by the anti-idiotypic antibody. The similarities between these T cell-bourne molecules, and immunoglobulin are inescapable. Both are disulphide-linked glycoproteins made up of 2 chains, both of which may vary in amino acid sequence. Secreted immunoglobulin is, of course, polyvalent, being composed of two or more of each type of chain, this contributes to the efficiency with which the molecule can bind polyvalent antigen or build precipitable lattices. Similar constraints do not apply to T cell-bound receptors, which do not seem to have a secreted form.