TY - JOUR
T1 - Topographic antigenic determinants recognized by monoclonal antibodies to sperm whale myoglobin
AU - Berzofsky, J. A.
AU - Buckenmeyer, G. K.
AU - Hicks, G.
AU - Gurd, F. R.
AU - Feldmann, R. J.
AU - Minna, J.
N1 - Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 1982
Y1 - 1982
N2 - Monoclonal antibodies of high affinity (~ 109 M-1) for sperm whale myoglobin were studied to pinpoint the antigenic determinants with which they interact. None of 6 different monoclonal antibodies tested reacted with any of the 3 CNBr cleavage fragments which encompass the whole sequence of myoglobin, an indication that they react with determinants present only on the native structure. To identify these sites, we compared the affinities of each antibody for a series of 14 mammalian myoglobins of known sequence and similar tertiary structure. Correlation of sequence differences with relative affinities allowed us, thus far, to identify critical antigenic residues recognized by 3 of the antibodies. Two of these antibodies recognize groups of residues which are far apart in primary structure but close together in the 3-dimensional structure of the native myoglobin molecule, i.e. topographic determinants. The third antibody distinguishes 140 Lys → Asn plus, probably, surface residues nearby. These determinants differ from previously reported antigenic sites on sperm whale myoglobin both in that they are topographic, rather than sequential, and in that almost all the critical residues recognized by these antibodies are outside the previously repoted sites. Monoclonal antibodies are sensitive to subtle changes, e.g. Glu → Asp, in the antigenic site.
AB - Monoclonal antibodies of high affinity (~ 109 M-1) for sperm whale myoglobin were studied to pinpoint the antigenic determinants with which they interact. None of 6 different monoclonal antibodies tested reacted with any of the 3 CNBr cleavage fragments which encompass the whole sequence of myoglobin, an indication that they react with determinants present only on the native structure. To identify these sites, we compared the affinities of each antibody for a series of 14 mammalian myoglobins of known sequence and similar tertiary structure. Correlation of sequence differences with relative affinities allowed us, thus far, to identify critical antigenic residues recognized by 3 of the antibodies. Two of these antibodies recognize groups of residues which are far apart in primary structure but close together in the 3-dimensional structure of the native myoglobin molecule, i.e. topographic determinants. The third antibody distinguishes 140 Lys → Asn plus, probably, surface residues nearby. These determinants differ from previously reported antigenic sites on sperm whale myoglobin both in that they are topographic, rather than sequential, and in that almost all the critical residues recognized by these antibodies are outside the previously repoted sites. Monoclonal antibodies are sensitive to subtle changes, e.g. Glu → Asp, in the antigenic site.
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M3 - Article
C2 - 6174516
AN - SCOPUS:0020050491
SN - 0021-9258
VL - 257
SP - 3189
EP - 3198
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 6
ER -