An MHC interaction site maps to the amino-terminal half of the T cell receptor α chain variable domain

We have used cloned T cell receptor (TCR) genes from closely related CD4 T cell lines to probe the interaction of the TCR with several specific major histocompatibility complex (MHC) class 11 ligands. Complementarity determining region 3 (CDR3) equivalents of both α and β TCR chains are required for antigen-MHC recognition. Our data provide novel information about the rotational orientation of TCR-MHC contacts in that exchange of the amino terminal portion of the TCR α chain containing the putative CDR1 and CDR2 regions results in both gain and loss of MHC class II specificity by the resulting receptor. These two TCRs differ primarily in recognition of polymorphisms in the second hypervariable region of the MHC class II α chain. These results document the involvement of CDR1 and/or CDR2 of the TCR α chain in MHC recognition and suggest a rotational orientation of this TCR to its MHC ligand.