Antigenicity of the Influenza Haemagglutinin Membrane Glycoprotein

Abstract

Antibodies which neutralize the infectivity of influenza viruses specifically react with the hemagglutinin membrane glycooroteins. These molecules, of which there are about 500 on each virus surface, serve to bind viruses to sialic acid-containing cellular receptors and to mediate fusion of virus and cellular membranes required for entry of virus genome-transcriptase complexes into the cell (reviewed in [11]. Neutralization probably involves inhibition of these functions. Hemaggluti- nins (HA) are trimers of molecular weight about 220,000 in which each monomer consists of two disulfide-linked glycopolypeptides, HA₁ and HA₂. The three-dimensional structure of the Hong Kong influenza X-31 HA has been determined crystallographically to 38 resolution [2], The trimer is 135 Å long and approximately triangular in cross-section, varying in radius from about 15 to 40 8. In each subunit the HA₁ glycopolypeptide chain extends from the base of the molecule near the virus membrane, through a fibrous stem to a peripheral region rich in β-structure, and then returns to the fibrous region and terminates about 30 8 from the membrane. The most prominent features of the part of the subunit composed of HA₂ residues are two antiparallel α-helices, one 29 Å long which proceeds distally to connect through an extended chain with the other helix, which stretches 76 Å back towards the membrane. This paper briefly describes studies of the antigenic variation of this molecule and its recognition by both antibodies and immune T cells.