Shared Fine Specificity between T-Cell Receptors and an Antibody Recognizing a Peptide / Major Histocompatibility Class I Complex

• Published in: Proceedings of the National Academy of Sciences - PNAS 1996-09, Vol.93 (19), p.10338-10342
• Main Authors: Stryhn, Anette, Andersen, Peter S., Pedersen, Lars O., Svejgaard, Arne, Holm, Arne, Thorpe, Christopher J., Fugger, Lars, Buus, Soren, Engberg, Jan
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Amino acids; Animals; Antibodies; Antibodies, Monoclonal; Antibody Specificity; Binding Sites; Crystal structure; Epitopes; Epitopes - chemistry; Epitopes - immunology; Histocompatibility Antigens Class I - chemistry; Histocompatibility Antigens Class I - immunology; Hybridomas; Immunity (Disease); Lymphoma, T-Cell - immunology; Major Histocompatibility Complex; Mice; Mice, Inbred AKR; Models, Molecular; Molecular chains; Molecular structure; Molecules; Peptide Fragments - chemistry; Peptide Fragments - immunology; Peptides; Protein Structure, Secondary; Receptors, Antigen, T-Cell - immunology; Recombinant Proteins; Rodents; T cell antigen receptors; T lymphocytes; T-Lymphocytes, Cytotoxic - immunology; Tumor Cells, Cultured; Vesicular stomatitis Indiana virus
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.93.19.10338

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, K$^{\text{k}}$-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 Ha$_{255-262}$-specific, K$^{\text{k}}$-restricted T cells, and of a unique antibody, pSAN, specific for the same peptide-MHC complex. Independently, a model of the Ha$_{255-262}$-K$^{\text{k}}$ 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.