SPECIFIC LOW-AFFINITY RECOGNITION OF MAJOR HISTOCOMPATIBILITY COMPLEX PLUS PEPTIDE BY SOLUBLE T-CELL RECEPTOR

THE T-cell receptor is necessary and sufficient for recognition of peptides presented by major histocompatibility complex molecules 1,2. Other adhesion molecules, like CD4 or CD8, play an auxiliary role in antigen recognition by T cells 3,4. Here we analyse T-cell receptor (TCR) binding using a soluble rather than a cell-bound receptor molecule. A TCR-immunoglobulin chimaera is constructed with the variable and the first constant regions of both the TCR alpha- and beta-chains linked to the immunoglobulin light-chain constant regions. This soluble TCR is expressed, assembled and secreted as an alpha-beta-heterodimer by a myeloma cell line transfected with the recombinant genes. Furthermore, the soluble TCR is biologically active: it specifically inhibits antigen-dependent activation of the relevant T-cell clones and thus discriminates between proper and irrelevant peptides presented by major histocompatibility complex molecules.