Replacements in the exposed loop of the T15 antibody VHCDR2 affect carrierrecognition of PC-containing pathogens

A panel of mutant antibodies of the phosphocholine (PC)-binding antibody, T 15, was tested for binding to PC-protein, Streptococcus pneumoniae, Trichin ella spiralis and Ascaris suum. Relative to wildtype T15, all the mutant an tibodies showed differential recognition of the panel of PC-associated anti gens. These mutant antibodies contain amino acid replacements in the CDR2 r egion of the heavy chain variable region, indicating the importance of CDR2 in recognition of carrier determinants. A model of T15 is shown that illus trates the strategic placement of mutations that could allow interaction wi th determinants associated with PC. A direct implication of this finding is that the T15 antibody combining site accommodates structures larger than p hosphocholine and that recognition of associated carrier determinants could be a significant force in shaping the immune response to PC-containing pat hogens. (C) 1999 Elsevier Science Ltd. All rights reserved.