Replacements in the exposed loop of the T15 antibody VH CDR2 affect carrier recognition of PC-containing pathogens.
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.
Department of Molecular Microbiology and Immunology, Oregon Health Sciences University, Portland 97201, USA.
M
M
Brown
G D
GD
Wiens
T
T
O'Hare
M P
MP
Stenzel-Poore
M B
MB
Rittenberg
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics / Q000276:immunology; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D000947:Antigens, Helminth / Q000276:immunology*; D017165:Ascaris suum / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000378:metabolism*; D007130:Immunoglobulin Idiotypes / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000276:immunology; D009194:Myeloma Proteins / Q000235:genetics; D010767:Phosphorylcholine / Q000276:immunology* / Q000378:metabolism*; D016415:Sequence Alignment; D013296:Streptococcus pneumoniae / Q000276:immunology; D017160:Trichinella spiralis / Q000276:immunology
D000942:Antigens, Bacterial; D000947:Antigens, Helminth; D007143:Immunoglobulin Heavy Chains; D007130:Immunoglobulin Idiotypes; D007135:Immunoglobulin Variable Region; D009194:Myeloma Proteins; C043925:myeloma protein TEPC15; D010767:Phosphorylcholine