Human IgA binds a diverse array of commensal bacteria.

Area of Science:

• Immunology
• Microbiome research
• Glycobiology

Background:

• Humans secrete grams of immunoglobulin A (IgA) daily in the gut.
• Unlike mice, humans have two IgA isotypes: IgA1 and IgA2.
• The distinct roles of IgA1 and IgA2 in interacting with the gut microbiota are not fully understood.

Purpose of the Study:

• To compare the binding patterns of human IgA1 and IgA2 to gut commensals.
• To determine the reactivity of IgA subclasses to glycan arrays.
• To characterize the binding profile of native human monoclonal IgA antibodies.

Main Methods:

• Analysis of polyclonal IgA subclass binding to commensal bacteria.
• Utilizing glycan arrays to assess IgA subclass specificity.
• Characterization of native human monoclonal IgA antibody reactivity.

Main Results:

• Most gut commensals are targeted by both IgA1 and IgA2 in the small intestine.
• Distinct populations of IgA1+IgA2+ and IgA1-IgA2+ bacteria exist in the colon.
• IgA2 shows preferential binding to Bacteroidetes and galactose-α terminated glycans.
• Gut-derived IgA monoclonal antibodies are cross-reactive but display private binding patterns.

Conclusions:

• Human IgA1 and IgA2 have differential interactions with the gut microbiota.
• IgA2 plays a specific role in targeting certain bacteria and glycans in the colon.
• Cross-reactivity and selectivity of IgA antibodies are explained by private anticarbohydrate-binding patterns.