Determinants of IgA binding to gut bacteria - more than species identity

Abstract

The bacteria in our gut are in close interaction with our immune system. IgA is a key driver of microbiota-immune interactions, but the exact mechanisms of IgA-gut bacteria binding are unknown. It has previously been shown that IgA does not bind every single bacterium even though they are genetically identical. Therefore, we hypothesized that IgA binding capacity is affected by bacterial characteristics beyond the genetic identity. IgA plasma cell-derived monoclonal antibodies (mAbs) were generated from healthy and Crohn's disease (CD) donors. The binding capacity of mAbs and endogenous-IgA was characterized for 37 human fecal samples. Out of these, the most distinct binding patterns in terms of high binding capacity were selected for cell sorting of the mAb-positive -and negative fractions and 16S rRNA-based characterization. De novo clustering of the β-diversity in our sample library did not align with mAb binding profiles. In addition, the binding specificity of these mAbs was not significantly related to molecular species. Thus, mAb binding shows major heterogeneity between human donors that cannot easily be explained by differences in microbiota composition. A possible explanation is that IgA-binding to gut bacteria is heavily dependent on factors other than species composition. Further experiments will aim at an in-depth characterization of mAb-binding to gut bacteria.