Cytotoxic and helper T-lymphocyte responses to antibody recognition regions on influenza virus hemagglutinin.

We have previously localized and synthesized twelve antibody recognition sites on influenza virus hemagglutinin (HA). These peptides correspond to exposed surface areas in the 3-D structure of HA. Using intact X31 virus as the immunogen, we have determined the recognition of these synthetic peptides by proliferative T-helper lymphocytes (ThL), delayed type hypersensitivity (DTH), and cytotoxic T-lymphocytes (CTL) responses. The responses to the individual determinants in each of these immune compartments were under separate Ir gene control. Conversely, using the peptides as immunogens, we have determined the ability of various peptide-specific antibodies (in outbred mice) and ThLs (in H-2k, H-2d, H-2s and H-2b mice) to recognize intact virus. Whereas most of the peptides primed the mice for an anti-peptide proliferative ThL response, only very few of these cross-reacted with the virus. The identity of the peptide(s) eliciting virus cross-reactive ThLs varied with the strain. The importance of antibody, ThL, CTL and DTH responses in protection against viral infection and in vaccine design is discussed.