Human cytotoxic T lymphocytes (CTL) recognize antigen in the form of short peptide fragments presented by Human Leukocyte Antigen (HLA) class 1 molecules. The HLA B27-restricted CTL response to Influenza A virus is directed against a single nine amino acid epitope within the viral nucleoprotein NP383-391. Influenza A-specific CTL lines and clones, generated from the peripheral blood of three unrelated individuals, exhibited remarkable fine specificity for NP383-391, failing to recognize synthetic variants containing single amino acid substitutions at positions 1, 4, 7 or 8. The sequences of rearranged T cell receptor (TCR) alpha and beta chain genes showed remarkable conservation of variable and joining gene segment usage, and also of non germline-encoded B chain residues proposed to interact with peptide, even between clones from unrelated individuals. Correlation of fine specificity for peptide with TCR alpha chain usage suggested a possible orientation for the TCR/HLA/peptide ternary complex in this immune response. The finding of restricted TCR usage in the HLA B27-restricted CTL response to influenza A virus has implications for the study and potential therapy of HLA B27 associated autoimmune disease. The TCR heterodimer from one clone was expressed in a rat basophil cell line and shown to confer specificity for HLA B27 + NP383-391. Influenza A-specific CTL were also shown to recognize bacterial superantigens in an MHC class II dependent but unrestricted manner. A rapid screening assay for candidate superantigens was developed and used to identify a novel superantigen produced by Clostridium perfringens. This superantigen was found to have a unique specificity for human TCRβ chains.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:335763 |
| Date | January 1993 |
| Creators | Bowness, Paul |
| Contributors | McMichael, Andrew J. |
| Publisher | University of Oxford |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://ora.ox.ac.uk/objects/uuid:c0733ea1-f5a2-4799-8969-49930ae9540d |
Page generated in 0.015 seconds