MUTATIONAL ANALYSIS OF POLYMERIC IMMUNOGLOBULIN RECEPTOR-LIGAND INTERACTIONS - EVIDENCE FOR THE INVOLVEMENT OF MULTIPLE COMPLEMENTARITY-DETERMINING REGION (CDR)-LIKE LOOPS IN RECEPTOR DOMAIN-I

The polymeric Ig receptor (pIgR) mediates the transport of IgA and IgM across a variety of mucosal epithelia. The ectodomain of this recepto r consists of five immunoglobulin-like domains (I-V), the first four b eing structurally similar to immunoglobulin variable regions, and the fifth to Ig constant regions. This study examines the structural featu res of the pIgR that participate in binding of the ligand, dimeric IgA (dIgA). Recent evidence suggests that a highly conserved region of th e first Ig-Like domain (domain I) may be important in this process (Ba kes, M. A., Kurosky, A., and Goldblum, R. M. (1991) J. Immunol. 147, 3 419-3426). In support of this hypothesis, molecular modeling of domain I places this conserved region in an exposed loop analogous to the CD R1 loop of Ig, suggesting that interactions between dIgA and the pIgR may be similar to those between antibodies and their cognate antigens. To test this hypothesis directly, we performed a mutagenic analysis o f all three CDR-like loops in domain I of the pIgR. We found that poin t mutations in multiple residues of CDR1 produced effects on IgA bindi ng ranging from minimal (90% of control) to profound (7%). In addition , we replaced regions corresponding to the CDR2 and CDR3 loops of doma in I with their counterparts from domain II (which does not bind IgA), which in both cases resulted in complete abrogation of IgA binding. T aken together, these data suggest that each of the three CDR-like loop s of domain I of the rabbit pIgR participates in the binding of dimeri c IgA.