Future Directions

In the last few years, several new three-dimensional structures have provided significant insight into mechanisms of mucosal immunity. However, several important issues remain unresolved and await further structural work. In particular, the structure of full-length SC (i.e., D1-D5 of the pIgR ectodomain) would be of great interest in order to better understand its interactions with IgA and CbpA from S. pneumoniae. In a similar vein, the structures of dimeric IgAand secretoryIgA (oratleaststructures of theFca-J chain-SC core of SIgA) will be important additions to the structural repertoire. Generation of sufficient quantities of pure, homogeneous dIgA or SIgA has been the limiting factor in these types of studies, although expression systems have been described recently for production of specific dIgA and SIgA (Chintalacharuvu and Morrison 1999; Corthesy 2002). Finally, structures ofvarious IgA-binding receptors and bacterial proteins, alone and in complex with IgA, combined with biophysical studies of their interactions will provide important insights into gut immunology and may lead to effective therapeutic strategies. For instance, understanding how the M cell receptor on Peyer's patches recognizes IgA2 could eventually lead to the development of effective oral vaccines, which would be of particular interest in developing regions of the world.

Acknowledgements The authors would like to thank Dr. Steve Perkins (University College London) for providing the coordinates of pentameric IgM.

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