T-CELL RECOGNITION OF THE POSTTRANSLATIONALLY CLEAVED INTERSUBUNIT REGION OF INFLUENZA-VIRUS HEMAGGLUTININ

The influenza virus hemagglutinin is synthesized as a single polypepti de chain, but upon maturation it will posttranslationally be modified by a host cell related trypsin-like enzyme. The enzymatic cleavage att acks the so-called intersubunit region of the molecule giving rise to covalently linked HA1 and HA2 subunits. An I-E(d)-restricted T cell ep itope was identified in the highly conserved intact intersubunit regio n of the influenza virus hemagglutinin. T cell recognition of a 25-mer synthetic peptide comprising the intact intersubunit region does not require further processing and the elimination of the intervening Arg residue coupling the fusion peptide to the C-terminal segment of HA1 d oes not abolish the T cell activating capacity. The fine specificity p attern of a T cell hybridoma similar to that of the polyclonal T cell response demonstrates that a single T cell receptor is able to recogni ze peptides of different sizes representing not only the uncleaved but also the cleaved form of this hemagglutinin region. Based on specific ity studies the epitope was localized to the C-terminal 11 amino acids of the HA1 subunit. The cross-reactivity of peptide-primed T cells wi th influenza virus infected antigen-presenting cells shows that fragme nts comprising the identified epitope of the intersubunit region can b e generated as a result of natural processing of the hemagglutinin mol ecule. As antigen-presenting cells are lacking the enzyme which is res ponsible for the posttranslational modification of newly synthesized h emagglutinin molecules, the role of immature viral proteins in immune recognition is discussed.