Predictable acquisition of a new MHC recognition specificity following expression of a transfected T-cell receptor β-chain gene

Abstract

Activation of mature T lymphocytes requires specific corecognition of antigen together with membrane-associated glycoprotein products of the major histocompatibility complex (MHC)¹. This dual specificity is determined by a single receptor structure consisting of a clone-specific αβ heterodlmer^2–8. Because both the α and β subunits possess unique combining-site-containing V regions⁹, it remains an open issue as to what contribution each of the two chains of the receptor makes to the antigen versus MHC recognition specificities of the complete dimer present on any given T cell or in the T-cell pool as a whole. In the present work, we have used DNA-mediated gene transfer to express a new α or β chain in a recipient murine T-cell hybridoma possessing a related antigen but distinct MHC specificity compared to the receptor-gene donor. Our results demonstrate that a β-gene transfected hybridoma expresses new receptors with a predictable hybrid specificity, establishing that the β chain has the predominant role in MHC molecule recognition in this model.