Mapping of antigenic changes in the haemagglutinin of Hong Kong influenza (H3N2) strains using a large panel of monoclonal antibodies

Abstract

A panel of 125 monoclonal antibodies (IgG) was raised against the haemagglutinin of an early representative of the Hong Kong (H3N2) subtype of influenza. They were classified into groups based on their cross-reactions with 16 other virus strains from the same subtype. This classification was performed using methods of numerical taxonomy. Statistical tests supported the validity of the grouping. Ten such groups were identified. Nine antibodies remained unclassified. The locations on the haemagglutinin molecule of amino acid residues influencing the binding of each antibody group were estimated. This was achieved by a study of antibody cross-reactive profiles, coupled with previously published locations of amino acid changes in the primary sequence of different haemagglutinins, and their positions in the tertiary structure of the molecule. The locations of the amino acids affecting antibody binding overlapped between the different antibody groups forming a continuous ring surrounding the probable cell-receptor pocket. The amino acids affecting the binding of each antibody group may or may not represent the actual antibody binding sites. The importance of the different sites of amino acid variation in the haemagglutinin during evolution of the virus is discussed.