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 (TCR) and immunoglobulins (Ig) are remarkably similar. Through recombinant, physical, and peptide-based immunological studies we demonstrated that rabbit antisera generated against a recombinant single-chain TCR (scTCR) react with defined peptide epitopes of their constituent TCR alpha 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 cross-reacted with the recombinant scTCR. Rabbit anti-lambda antibodies purified on an scTCR affinity column bound to T-cell lines and to T and B lymphocytes from peripheral blood. Circular dichroism analysis demonstrated plots characteristic of beta-sheets for both Mcg and recombinant scTCR. Antisera directed against TCR alpha-chain synthetic peptides reacted with scTCR, Mcg lambda light-chain protein, synthetic peptides from regions of sequence homology in beta-chains, and Mcg. Based upon this homology and the serological cross-reactions which reflect conformational determinants, we suggest that the V alpha/V beta antigen-binding domain of this particular monoclonal scTCR construct is substantially similar to the conformational structure of lambda light chains.