Replacements in the exposed loop of the T15 antibody VH CDR2 affect carrier recognition of PC-containing pathogens

Abstract

A panel of mutant antibodies of the phosphocholine (PC)-binding antibody, T15, was tested for binding to PC-protein, Streptococcus pneumoniae, Trichinella spiralis and Ascaris suum. Relative to wildtype T15, all the mutant antibodies showed differential recognition of the panel of PC-associated antigens. These mutant antibodies contain amino acid replacements in the CDR2 region of the heavy chain variable region, indicating the importance of CDR2 in recognition of carrier determinants. A model of T15 is shown that illustrates the strategic placement of mutations that could allow interaction with determinants associated with PC. A direct implication of this finding is that the T15 antibody combining site accommodates structures larger than phosphocholine and that recognition of associated carrier determinants could be a significant force in shaping the immune response to PC-containing pathogens.