Mapping of the extracellular binding regions of the human interleukin-8 type B receptor

This study was undertaken to define the regions of the human interleukin-8 type B receptor (IL8RB) which are critical for binding the ligands interleukin-8, NAP-2 and GRO alpha. Peptides corresponding to the N-terminus region and the first extracellular loop of the receptor demonstrated statistically significant (p=0.001) inhibition of IL-8 control binding levels (inhibition levels of 73.0+/-5.1% and 89.9+/-2.2% respectively). In contrast, NAP-2 binding was inhibited only by the peptide representing the first extracellular loop (63.2+/-2.3%), while GRO alpha binding was inhibited by portions of the N-terminus (49.7+/-14.9% and 41.8+/-14.9%), but not the first extracellular loop. We suggest that: a) the chemokine receptor IL8RB, known to bind three related ligands with high affinity, seems to do so via distinct contact points and b.) the first extracellular loop is significant in the binding event. (C) 1997 Academic Press.