tetano
Editor, Senior Moderator
PLoS Pathog. 2019 Jan 3;15(1):e1007427. doi: 10.1371/journal.ppat.1007427. eCollection 2019 Jan.
[h=1]IgA tetramerization improves target breadth but not peak potency of functionality of anti-influenza virus broadly neutralizing antibody.[/h] Saito S[SUP]1,[/SUP][SUP]2[/SUP], Sano K[SUP]1,[/SUP][SUP]3[/SUP], Suzuki T[SUP]1[/SUP], Ainai A[SUP]1[/SUP], Taga Y[SUP]4[/SUP], Ueno T[SUP]4[/SUP], Tabata K[SUP]1[/SUP], Saito K[SUP]1[/SUP], Wada Y[SUP]1[/SUP], Ohara Y[SUP]1[/SUP], Takeyama H[SUP]5[/SUP], Odagiri T[SUP]2[/SUP], Kageyama T[SUP]2[/SUP], Ogawa-Goto K[SUP]4[/SUP], Multihartina P[SUP]6[/SUP], Setiawaty V[SUP]6[/SUP], Pangesti KNA[SUP]6[/SUP], Hasegawa H[SUP]1,[/SUP][SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Mucosal immunoglobulins comprise mainly secretory IgA antibodies (SIgAs), which are the major contributor to pathogen-specific immune responses in mucosal tissues. These SIgAs are highly heterogeneous in terms of their quaternary structure. A recent report shows that the polymerization status of SIgA defines their functionality in the human upper respiratory mucosa. Higher order polymerization of SIgA (i.e., tetramers) leads to a marked increase in neutralizing activity against influenza viruses. However, the precise molecular mechanisms underlying the effects of SIgA polymerization remain elusive. Here, we developed a method for generating recombinant tetrameric monoclonal SIgAs. We then compared the anti-viral activities of these tetrameric SIgAs, which possessed variable regions identical to that of a broadly neutralizing anti-influenza antibody F045-092 against influenza A viruses, with that of monomeric IgG or IgA. The tetrameric SIgA showed anti-viral inhibitory activity superior to that of other forms only when the antibody exhibits low-affinity binding to the target. By contrast, SIgA tetramerization did not substantially modify anti-viral activity against targets with high-affinity binding. Taken together, the data suggest that tetramerization of SIgA improved target breadth, but not peak potency of antiviral functions of the broadly neutralizing anti-influenza antibody. This phenomenon presumably represents one of the mechanisms by which SIgAs present in human respiratory mucosa prevent infection by antigen-drifted influenza viruses. Understanding the mechanisms involved in cross neutralization of viruses by SIgAs might facilitate the development of vaccine strategies against viral infection of mucosal tissues.
PMID: 30605488 DOI: 10.1371/journal.ppat.1007427
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[h=1]IgA tetramerization improves target breadth but not peak potency of functionality of anti-influenza virus broadly neutralizing antibody.[/h] Saito S[SUP]1,[/SUP][SUP]2[/SUP], Sano K[SUP]1,[/SUP][SUP]3[/SUP], Suzuki T[SUP]1[/SUP], Ainai A[SUP]1[/SUP], Taga Y[SUP]4[/SUP], Ueno T[SUP]4[/SUP], Tabata K[SUP]1[/SUP], Saito K[SUP]1[/SUP], Wada Y[SUP]1[/SUP], Ohara Y[SUP]1[/SUP], Takeyama H[SUP]5[/SUP], Odagiri T[SUP]2[/SUP], Kageyama T[SUP]2[/SUP], Ogawa-Goto K[SUP]4[/SUP], Multihartina P[SUP]6[/SUP], Setiawaty V[SUP]6[/SUP], Pangesti KNA[SUP]6[/SUP], Hasegawa H[SUP]1,[/SUP][SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Mucosal immunoglobulins comprise mainly secretory IgA antibodies (SIgAs), which are the major contributor to pathogen-specific immune responses in mucosal tissues. These SIgAs are highly heterogeneous in terms of their quaternary structure. A recent report shows that the polymerization status of SIgA defines their functionality in the human upper respiratory mucosa. Higher order polymerization of SIgA (i.e., tetramers) leads to a marked increase in neutralizing activity against influenza viruses. However, the precise molecular mechanisms underlying the effects of SIgA polymerization remain elusive. Here, we developed a method for generating recombinant tetrameric monoclonal SIgAs. We then compared the anti-viral activities of these tetrameric SIgAs, which possessed variable regions identical to that of a broadly neutralizing anti-influenza antibody F045-092 against influenza A viruses, with that of monomeric IgG or IgA. The tetrameric SIgA showed anti-viral inhibitory activity superior to that of other forms only when the antibody exhibits low-affinity binding to the target. By contrast, SIgA tetramerization did not substantially modify anti-viral activity against targets with high-affinity binding. Taken together, the data suggest that tetramerization of SIgA improved target breadth, but not peak potency of antiviral functions of the broadly neutralizing anti-influenza antibody. This phenomenon presumably represents one of the mechanisms by which SIgAs present in human respiratory mucosa prevent infection by antigen-drifted influenza viruses. Understanding the mechanisms involved in cross neutralization of viruses by SIgAs might facilitate the development of vaccine strategies against viral infection of mucosal tissues.
PMID: 30605488 DOI: 10.1371/journal.ppat.1007427
Free full text