Shared fine specificity between T-cell receptors and an antibody recognizing a peptide/major histocompatibility class I complex.
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.
Stryhn
A
A
Department of Experimental Immunology, University of Copenhagen, Denmark.
Andersen
P S
PS
Pedersen
L O
LO
Svejgaard
A
A
Holm
A
A
Thorpe
C J
CJ
Fugger
L
L
Buus
S
S
Engberg
J
J
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D001665:Binding Sites; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000276:immunology*; D016399:Lymphoma, T-Cell / Q000276:immunology*; D008285:Major Histocompatibility Complex; D051379:Mice; D008806:Mice, Inbred AKR; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D017433:Protein Structure, Secondary; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D011994:Recombinant Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014721:Vesicular stomatitis Indiana virus
D000911:Antibodies, Monoclonal; D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins