Major contribution of the beta chain to the antigen specificity of a T cell receptor

Abstract

T cell receptors (TCR) recognize peptides presented by major histocompatibility complex (MHC) molecules on the surface of cells. Sequence homology between the variable regions of the T cell receptor and of antibodies suggests that similarly-folded domains participate in ligand binding in both cases. However, most current models assume that both TCR chains (alpha and beta) are required for specific binding, whereas the heavy chain alone can confer specificity on many antibodies. We have therefore constructed chimeric molecules with alpha and beta from two different TCR, one restricted by the class II MHC protein, Ek, and the other by the class I MHC, Kd. The beta chain alone was sufficient for specific recognition of a peptide, Cw3, bound to Kd, but the alpha chain contributed to the overall avidity. These results suggest that other TCR may recognize their ligands primarily through the beta chain.