|
|
|
|
|
|
|
||
J. Exp. Med.,
Volume 189, Number 4, February 15, 1999 747-752
3 Domain Motif
Directs Polymeric Ig Receptor-mediated Secretion
By
From the Molecular Immunogenetics Program, Oklahoma Medical Research Foundation, Oklahoma
City, Oklahoma 73104
Polymeric immunoglobulins provide immunological protection at mucosal surfaces to which
they are specifically transported by the polymeric immunoglobulin receptor (pIgR). Using a
panel of human IgA1/IgG1 constant region "domain swap" mutants, the binding site for the
pIgR on dimeric IgA (dIgA) was localized to the C
3 domain. Selection of random peptides
for pIgR binding and comparison with the IgA sequence suggested amino acids 402-410 (QEPSQGTTT), in a predicted exposed loop of the C3 domain, as a potential binding site.
Alanine substitution of two groups of amino acids in this area abrogated the binding of dIgA to
pIgR, whereas adjacent substitutions in a 
-strand immediately NH2-terminal to this loop had
no effect. All pIgR binding IgA sequences contain a conserved three amino acid insertion, not
present in IgG, at this position. These data localize the pIgR binding site on dimeric human
IgA to this loop structure in the C3 domain, which directs mucosal secretion of polymeric
antibodies. We propose that it may be possible to use a pIgR binding motif to deliver antigen-specific dIgA and small-molecule drugs to mucosal epithelia for therapy.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
| TABLE OF CONTENTS |
|
