INTERACTION OF PIGEON CYTOCHROME C-(43-58) PEPTIDE ANALOGS WITH EITHER T-CELL ANTIGEN RECEPTOR OR I-AB MOLECULE

We determined that a pigeon cytochrome c-derived peptide, p43-58, poss esses two anchor residues, 46 and 54, for binding with the I-A(b) mole cule that are compatible to the position 1 (P1) and position 9 (P9) of the core region in the major histocompatibility complex (MHC) class I I binding peptides, respectively. In the present study to analyze each binding site between P1 and P9 of p43-58 to either I-A(b) or T cell a ntigen receptor (TCR), we investigated T cell responses to a series of peptides (P2K, P3K, P4K, P5K, P6K, P7K, and P8E) that sequentially su bstituted charged amino acid residues for the residues at P2 to P8 of p43-58, T cells from C57BL/10 (I-A(b)) mice immunized with P4K or P6K did not mount appreciable proliferative responses to the immunogens, b ut those primed with other peptides (P2K, P3K, P5K, P7K, and P8E) show ed substantial responses in an immunogen-specific manner, It was demon strated by binding studies that P1 and P9 functioned as main anchors a nd P4 and P6 functioned as secondary anchors to I-A(b), Analyses of V beta usage of T cell lines specific for these analogs suggested that F 8 interacts with the complementarity-determining region 1 (CDR1)/CDR2 of the TCR beta chain, Furthermore, sequencing of the TCR on T cell hy bridomas specific for these analogs indicated that P5 interacts with t he CDR3 of the TCR beta chain, The present findings are consistent wit h the three-dimensional structure of the trimolecular complex that has been reported for TCR/peptide/MHC class I molecules.