Overlapping cytotoxic T-lymphocyte and B-cell antigenic sites on the influenza virus H5 hemagglutinin—Hioe 1990
An H5 HA-specific CTL clone was tested for its ability to detect monoclonal antibody-selected HA variants of influenza virus A/Turkey/Ontario/7732/66 (H5N9) to determine its recognition site. 51Cr release assays with variations revealed a CTL epitope near H5 HA residue 168. Several overlapping peptides were generated and evaluated for CTL recognition to better characterize the epitope. H5 HA residues 158–169 were the CTL clone's minimal peptide. This CTL epitope, also a significant B-cell epitope on H3 HA, is near the distal terminal of the HA molecule. A single mutation at position 168 (Lys to Glu) in the H5 HA variants eliminated CTL recognition, which was previously shown to be necessary for B-cell recognition (M. Philpott, C. Hioe, M. Sheerar, and V. S. Hinshaw, J. Virol. 64:2941-2947, 1990). The CTL clone recognized the HA of A/Turkey/Ireland/1378/83 (H5N8) but not that of A/Chicken/Pennsylvania/1370/83 (H5N2), even though these viruses have identical HA molecules (M. Philpott, B. C. Easterday, and V.S. Hinshaw, J. Virol. 63:3453-3458, 1989). Mutations in this region of the HA molecule were associated with attenuation of the highly virulent A/Turkey/Ontario/7732/66 (H5N9) (M. Philpot These findings imply that non-CTL epitope variations affected CTL recognition of the entire HA molecule. These investigations show that the H5 HA site is crucial for CTL and B-cell identification and viral pathogenesis.
Hioe, C. E., Dybdahl-Sissoko, N., Philpott, M., & Hinshaw, V. S. (1990). Overlapping cytotoxic T-lymphocyte and B-cell antigenic sites on the influenza virus H5 hemagglutinin. Journal of virology, 64(12), 6246–6251. https://doi.org/10.1128/JVI.64.12.6246-6251.1990
