Human IgA binds a diverse array of commensal bacteria

Delphine Sterlin (1, 2) , Jehane Fadlallah (1, 2) , Olivia Adams (3) , Claire Fieschi (4, 5) , Christophe Parizot (1, 2) , Karim Dorgham (1, 2) , Asok Rajkumar (1, 2) , Gaëlle Autaa (1, 2) , Hela El-Kafsi (1, 2) , Jean-Luc L Charuel (1, 2) , Catherine Juste (6, 7, 8, 9) , Friederike Jönsson (10) , Thomas Candela (11, 9, 6) , Hedda Wardemann (12) , Alexandra Aubry (1, 2) , Carmen Capito (11, 13, 9) , Hélène Brisson (2, 1) , Christophe Trésallet (2) , Richard D Cummings (14) , Martin Larsen (1, 2) , Hans Yssel (1, 2) , Stephan von Gunten (3) , Guy Gorochov (1, 2)

1 CIMI - Centre d'Immunologie et des Maladies Infectieuses
2 CHU Pitié-Salpêtrière [AP-HP]
3 UNIBE - Universität Bern / University of Bern
4 Service d'Immunopathologie [Hôpital Saint-Louis, Paris]
5 UPD7 - Université Paris Diderot - Paris 7
6 MICALIS - MICrobiologie de l'ALImentation au Service de la Santé
7 AgroParisTech
8 INRA - Institut National de la Recherche Agronomique
9 Université Paris-Saclay
10 Anticorps en thérapie et pathologie - Antibodies in Therapy and Pathology
11 UBaPS - Bactéries, Pathogènes et Santé
12 DKFZ - German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg]
13 UP11 - Université Paris-Sud - Paris 11
14 HMS - Harvard Medical School [Boston]

In humans, several grams of IgA are secreted every day in the intestinal lumen. While only one IgA isotype exists in mice, humans secrete IgA1 and IgA2, whose respective relations with the microbiota remain elusive. We compared the binding patterns of both polyclonal IgA subclasses to commensals and glycan arrays and determined the reactivity profile of native human monoclonal IgA antibodies. While most commensals are dually targeted by IgA1 and IgA2 in the small intestine, IgA1+IgA2+ and IgA1-IgA2+ bacteria coexist in the colon lumen, where Bacteroidetes is preferentially targeted by IgA2. We also observed that galactose-α terminated glycans are almost exclusively recognized by IgA2. Although bearing signs of affinity maturation, gut-derived IgA monoclonal antibodies are cross-reactive in the sense that they bind to multiple bacterial targets. Private anticarbohydrate-binding patterns, observed at clonal level as well, could explain these apparently opposing features of IgA, being at the same time cross-reactive and selective in its interactions with the microbiota.

Domaines: Immunologie

Delphine Sterlin, Jehane Fadlallah, Olivia Adams, Claire Fieschi, Christophe Parizot, et al.. Human IgA binds a diverse array of commensal bacteria. Journal of Experimental Medicine, 2020, 217 (3), pp.e20181635. ⟨10.1084/jem.20181635⟩. ⟨hal-02433421⟩