PHYSICAL AND EPITOPE ANALYSIS OF A RECOMBINANT HUMAN T-CELL RECEPTOR V-ALPHA V-BETA CONSTRUCT SUPPORT THE SIMILARITY TO IMMUNOGLOBULIN/

The genetic organization and protein structure of T-cell receptors (TC R) and immunoglobulins (Ig) are remarkably similar. Through recombinan t, physical, and peptide-based immunological studies we demonstrated t hat rabbit antisera generated against a recombinant single-chain TCR ( scTCR) react with defined peptide epitopes of their constituent TCR al pha and beta chains. These antisera cross-react with the lambda light- chain Mcg as well as with peptides duplicating its covalent structure. Conversely, rabbit antisera generated to human lambda light chains cr oss-reacted with the recombinant scTCR. Rabbit anti-lambda antibodies purified on an scTCR affinity column bound to T-cell lines and to T an d B lymphocytes from peripheral blood. Circular dichroism analysis dem onstrated plots characteristic of beta-sheets for both Meg and recombi nant scTCR. Antisera directed against TCR alpha-chain synthetic peptid es reacted with scTCR, Meg lambda light-chain protein, synthetic pepti des from regions of sequence homology in beta-chains, and Mcg. Based u pon this homology and the serological cross-reactions which reflect co nformational determinants, we suggest that the V alpha/V beta antigen- binding domain of this particular monoclonal scTCR construct is substa ntially similar to the conformational structure of lambda light chains .