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Epitope mapping of human factor IX inhibitor antibodies
Author(s) -
Takahashi Isao,
Mizumo Shinichi,
Kamiya Tadashi,
Takamatsu Junki,
Saito Hidehiko
Publication year - 1994
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1994.tb04992.x
Subject(s) - neutralization , factor ix , epitope , antibody , microbiology and biotechnology , monoclonal antibody , haemophilia b , chemistry , cleavage (geology) , peptide , epitope mapping , haemophilia a , virology , haemophilia , biology , biochemistry , immunology , paleontology , genetics , fracture (geology)
Summary. We have determined the location of epitopes on the factor IX for three haemophilia B inhibitor antibodies (HB‐1, HB‐3, HB‐7) and a monoclonal anti‐factor IX inhibitory antibody (designated 65–10). The main binding region of HB‐1, HB‐3 and HB‐7 was 155 YVNSTEAETI 164 (residues 155–164), 167 NITQSTQSFN 176 and 156 VNSTEAETI 164 , respectively. The binding region of 65–10 was 168 ITQSTQSFNDFTRVV 182 , which included the cleavage site ( 180 R‐V 181 ) for activation by factor XIa. By neutralization experiments using two peptides, 156 VNSTEAETI 164 and 167 NITQSTQSFN 176 , the degree of neutralization of anti‐factor IX IgG purified by protein A was determined. Neutralization of three antibodies, HB‐1, HB‐3 and HB‐7, in the presence of 10m m of the peptides 156 VNSTEAETI 164 was 30.1%, 0% and 10.8%, respectively, and in the presence of 4 m m of 167 NITQSTQSFN 176 it was 0%, 13.5% and 17.3%, respectively. On the other hand, when plasmas of patients instead of purified IgG were used for neutralization, 10 m m of 156 VNSTEAETI 164 and 4 m m of 167 NITQSTQSFN 176 failed to neutralize the inhibitor in the plasmas.