Single amino acid residues in a synthetic peptide of influenza haemagglutinin, HA 1 177-199, distinguish I-Ad- and I-Ed-restricted T-cell epitopes

Abstract

A majority of Iad-restricted, CD4+ T-cell clones, derived from BALB/c mice infected with X31 (H3N2) influenza virus and specific for the HA 1 subunit of the viral haemagglutinin (HA), has previously been shown to recognize the synthetic peptide HA 1 177-199, corresponding to the primary amino acid sequence of a major antibody binding site. Here it is demonstrated that both I-Ad- and I-Ed-restricted T-cell clones recognize HA 1 177-199, and that inter- and intra-allelic differences in Iad-restricted recognition are defined by single amino acid residues. A panel of truncated HA 1 synthetic peptides defined three distinct but overlapping CD4+ epitopes within the common antigenic site (HA 1 177-199): two I-Ad-restricted epitopes mapped within HA 1 186-198 and HA 1 177-199, and peptide HA 1 178-195 identified an I-Ed-restricted epitope. Moreover, fine specificity differences in the recognition of synthetic peptides, truncated at the carboxy terminus of HA 1 177-199, identified residues HA 1 A 198 and HA 1 S 199 as being critical for defining inter- and intra-allelic differences, respectively, in the Iad-restricted T-cell recognition of HA.