REACTIONS OF ANTIIMMUNOGLOBULIN SERA WITH SYNTHETIC T-CELL RECEPTOR PEPTIDES - IMPLICATIONS FOR THE 3-DIMENSIONAL STRUCTURE AND FUNCTION OF THE TCR BETA-CHAIN

Abstract

The derived amino acid sequence of the human TCR beta chain shows considerable homology to Ig lambda light chains in its variable (V) and constant (C) domains, and in its joining segment (J). We assessed the cross-reactivity between TCR beta chains and Ig light chains by synthesizing a set of nested, overlapping 16-mer peptides that duplicated the sequence that corresponds to the continuous VDJC sequence of TCR beta chain and determining the capacity of rabbit antisera to human or murine Igs to react with these peptides. The reactivities we observed were consistent with homologies to lambda and kappa light chains. The strongest reactivity in ELISA binding and competitive inhibition was with a peptide that corresponds to the 'switch peptide' of light chains. The sequence is encoded by the C-terminal region of the J segment (Fr4) and the N-terminus of the C region. Other regions reactive with anti-light chain sera corresponded respectively to CDR1 and Fr3 segments of the V region, and a segment of the constant region predicted to loop out of the tight globular structure. The peptide immunochemical results, coupled with the identification of specific regions of sequence correspondence between TCR beta and the characterized lambda light chain Mcg, allowed us to develop a three-dimensional model of the beta chain consistent with its role in antigen recognition and response to superantigens.