PREDICTED COMPLEMENTARITY-DETERMINING REGIONS OF THE T-CELL ANTIGEN RECEPTOR DETERMINE ANTIGEN-SPECIFICITY

The antigen receptor on T cells (TCR) has been predicted to have a str ucture similar to a membrane-anchored form of an immunoglobulin F(ab) fragment. Virtually all of the conserved amino acids that are importan t for inter- and intramolecular interactions in the V-H-V-L pair are a lso conserved in the TCR V alpha and V beta chains. A molecular model of the TCR has been constructed by homology and we have used the infor mation from this, as well as the earlier structural predictions of oth ers, to study the basis for specificity. Specifically, regions of a TC R cloned from an antigen-specific T cell were stitched into the corres ponding framework of a second TCR. Results indicate that the substitut ion of amino acid sequences corresponding to the complementarity deter mining regions (CDRs) of immunoglobulin can convey the specificity for antigen and major histocompatibility complex molecules. These data ar e consistent with a role, but not an exclusive role, for CDR3 in antig en peptide recognition.