License to Clump: Secretory IgA Structure-Function Relationships Across Scales.

Secretory antibodies are the only component of our adaptive immune system capable of attacking mucosal pathogens topologically outside of our bodies. All secretory antibody classes are (a) relatively resistant to harsh proteolytic environments and (b) polymeric. Recent elucidation of the structure of secretory IgA (SIgA) has begun to shed light on SIgA functions at the nanoscale. We can now begin to unravel the structure-function relationships of these molecules, for example, by understanding how the bent conformation of SIgA enables robust cross-linking between adjacent growing bacteria. Many mysteries remain, such as the structural basis of protease resistance and the role of noncanonical bacteria-IgA interactions. In this review, we explore the structure-function relationships of IgA from the nano- to the metascale, with a strong focus on how the seemingly banal "license to clump" can have potent effects on bacterial physiology and colonization.