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.
Holzer B, Rijal P, McNee A, Paudyal B, Martini V, Clark B, Manjegowda T, Salguero FJ, Bessell E, Schwartz JC, Moffat K, Pedrera M, Graham SP, Noble A, Placido MB, La Ragione RM, Mwangi W, Beverley P, McCauley JW, Daniels RS, Hammond JA, Townsend AR, Tchilian E.
PLoS Pathog. 2021 Aug 04;17(8):e1009815. doi: 10.1371/journal.ppat.1009815. eCollection 2021 Aug.
PMID: 34347851
