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, possesses two anchor residues, 46 and 54, for binding with the I-Ab molecule that are compatible to the position 1 (P1) and position 9 (P9) of the core region in the major histocompatibility complex (MHC) class II binding peptides, respectively. In the present study to analyze each binding site between P1 and P9 of p43-58 to either I-Ab or T cell antigen receptor (TCR), we investigated T cell responses to a series of peptides (P2K, P3K, P4K, P5K, P6K, P7K, and P8E) that sequentially substituted charged amino acid residues for the residues at P2 to P8 of p43-58. T cells from C57BL/10 (I-Ab) mice immunized with P4K or P6K did not mount appreciable proliferative responses to the immunogens, but those primed with other peptides (P2K, P3K, P5K, P7K, and P8E) showed substantial responses in an immunogen-specific manner. It was demonstrated by binding studies that P1 and P9 functioned as main anchors and P4 and P6 functioned as secondary anchors to I-Ab. Analyses of Vbeta usage of T cell lines specific for these analogs suggested that P8 interacts with the complementarity-determining region 1 (CDR1)/CDR2 of the TCR beta chain. Furthermore, sequencing of the TCR on T cell hybridomas specific for these analogs indicated that P5 interacts with the CDR3 of the TCR beta chain. The present findings are consistent with the three-dimensional structure of the trimolecular complex that has been reported for TCR/peptide/MHC class I molecules.
Itoh
Y
Y
Section of Pathology, Institute of Immunological Science, Hokkaido University, Sapporo 060, Japan.
Kajino
K
K
Ogasawara
K
K
Takahashi
A
A
Namba
K
K
Negishi
I
I
Matsuki
N
N
Iwabuchi
K
K
Kakinuma
M
M
Good
R A
RA
Onoé
K
K
D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D010856:Columbidae; D003574:Cytochrome c Group / Q000276:immunology*; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*; D011485:Protein Binding; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D017422:Sequence Analysis, DNA; D013601:T-Lymphocytes / Q000276:immunology*
D003574:Cytochrome c Group; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta