Inhibitory effects of monoclonal antibodies to a synthetic peptide of influenza haemagglutinin on the processing and presentation of viral antigens to class II-restricted T-cell clones

Monoclonal Antibodies (mAb) prepared against a synthetic peptide of Influenza Virus haemagglutinin (HA), containing a known T-cell determinant, were used to examine the mechanism of antigen-induced activation of HA-specific class II-restricted T-cell clones. Previous studies had shown that T-cell clones, established from mice primed by Infection with Influenza Virus, recognize variable antibody binding region of HA, including a determinant formed from residues within the sequence HA1 48-68. MAb to the synthetic peptide, p48-68, recognized purified HA and whole virus in an ELISA, and their specificity pattern for natural variant viruses was similar to that described for the T-cell clones specific for the same peptide. The anti-peptide mAb inhibited peptide or virus-induced proliferation of the peptide specific T-cell clones (but has no effect on a unrelated HA-specific clone), whereas mAb to the native HA molecule inhibited virus but not peptide-induced T-cell activation. In addition, the anti-peptide mAb showed significant inhibition of T-cell proliferation to peptide or virus pulsed antigen-presenting cell (APC). The results suggest that the anti-HA mAb affect antigen induced T-cell activation simply through blocking virus uptake by the APC, whereas the anti-peptide Antibodies, which appear to recognize the same determinant on the peptide and the processed antigen, mediate their effect at the level of antigen presentation.