Topographic antigenic determinants recognized by monoclonal antibodies to sperm whale myoglobin

J. A. Berzofsky, G. K. Buckenmeyer, G. Hicks, F. R. Gurd, R. J. Feldmann, J. Minna

Research output: Contribution to journalArticlepeer-review

121 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3189-3198
Number of pages10
JournalJournal of Biological Chemistry
Volume257
Issue number6
StatePublished - 1982

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Topographic antigenic determinants recognized by monoclonal antibodies to sperm whale myoglobin'. Together they form a unique fingerprint.

Cite this