TY - JOUR
T1 - Shared fine specificity between T-cell receptors and an antibody recognizing a peptide/major histocompatibility class I complex
AU - Stryhn, A
AU - Andersen, P S
AU - Pedersen, L O
AU - Svejgaard, A
AU - Holm, A
AU - Thorpe, C J
AU - Fugger, L
AU - Buus, S
AU - Engberg, J
N1 - Keywords: Amino Acid Sequence; Animals; Antibodies, Monoclonal; Antibody Specificity; Binding Sites; Epitopes; Histocompatibility Antigens Class I; Lymphoma, T-Cell; Major Histocompatibility Complex; Mice; Mice, Inbred AKR; Models, Molecular; Peptide Fragments; Protein Structure, Secondary; Receptors, Antigen, T-Cell; Recombinant Proteins; T-Lymphocytes, Cytotoxic; Tumor Cells, Cultured; Vesicular stomatitis Indiana virus
PY - 1996
Y1 - 1996
N2 - Cytotoxic T cells recognize mosaic structures consisting of target peptides embedded within self-major histocompatibility complex (MHC) class I molecules. This structure has been described in great detail for several peptide-MHC complexes. In contrast, how T-cell receptors recognize peptide-MHC complexes have been less well characterized. We have used a complete set of singly substituted analogs of a mouse MHC class I, Kk-restricted peptide, influenza hemagglutinin (Ha)255-262, to address the binding specificity of this MHC molecule. Using the same peptide-MHC complexes we determined the fine specificity of two Ha255-262-specific, Kk-restricted T cells, and of a unique antibody, pSAN, specific for the same peptide-MHC complex. Independently, a model of the Ha255-262-Kk complex was generated through homology modeling and molecular mechanics refinement. The functional data and the model corroborated each other showing that peptide residues 1, 3, 4, 6, and 7 were exposed on the MHC surface and recognized by the T cells. Thus, the majority, and perhaps all, of the side chains of the non-primary anchor residues may be available for T-cell recognition, and contribute to the stringent specificity of T cells. A striking similarity between the specificity of the T cells and that of the pSAN antibody was found and most of the peptide residues, which could be recognized by the T cells, could also be recognized by the antibody.
AB - Cytotoxic T cells recognize mosaic structures consisting of target peptides embedded within self-major histocompatibility complex (MHC) class I molecules. This structure has been described in great detail for several peptide-MHC complexes. In contrast, how T-cell receptors recognize peptide-MHC complexes have been less well characterized. We have used a complete set of singly substituted analogs of a mouse MHC class I, Kk-restricted peptide, influenza hemagglutinin (Ha)255-262, to address the binding specificity of this MHC molecule. Using the same peptide-MHC complexes we determined the fine specificity of two Ha255-262-specific, Kk-restricted T cells, and of a unique antibody, pSAN, specific for the same peptide-MHC complex. Independently, a model of the Ha255-262-Kk complex was generated through homology modeling and molecular mechanics refinement. The functional data and the model corroborated each other showing that peptide residues 1, 3, 4, 6, and 7 were exposed on the MHC surface and recognized by the T cells. Thus, the majority, and perhaps all, of the side chains of the non-primary anchor residues may be available for T-cell recognition, and contribute to the stringent specificity of T cells. A striking similarity between the specificity of the T cells and that of the pSAN antibody was found and most of the peptide residues, which could be recognized by the T cells, could also be recognized by the antibody.
M3 - Journal article
C2 - 8816801
SN - 0027-8424
VL - 93
SP - 10338
EP - 10342
JO - Proceedings of the National Academy of Science of the United States of America
JF - Proceedings of the National Academy of Science of the United States of America
IS - 19
ER -