Influenza A Virus-Specific H-2dRestricted Cross-Reactive Cytotoxic T Lymphocyte Epitope(s) Detected in the Hemagglutinin HA2 Subunit of A/Udorn/72

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BALB/c mice immunized with a vaccinia virus recombinant expressing the influenza A virus (A/Udorn/72; subtype H3) hemagglutinin HA2 (H3HA2) induced a strong CD8+cytotoxic T lymphocyte (CTL) response which wasH-2d-restricted. Two peptides, derived from the primary sequence of the H3HA2 and consistent with the predictive motif for Kd-restricted epitopes, were tested for their ability to be presented to the CTLs by P815 cells. Peptides corresponding to the amino acids93SYNAELLVAL102and181GYKDWILWI189of the HA2 primary sequence sensitized target cells for lysis by the HA2-specific CTLs. Secondaryin vitrostimulation with dendritic cells as a source of antigen presenting cells treated with peptide 93-102, or infected with recombinant vaccinia virus (HA2-VACC), induced type A cross-reactive CTLs from A/Udorn/72 immune spleen cells. This CD8+CTL epitope overlaps with an H3HA2 I-Ad-restricted T helper epitope 96-104 recently reported by others. The H3HA2 epitope described here is the first CTL epitope in the influenza hemagglutinin which is found in all three subtypes of influenza A virus.