Attempts to locate residues in complementarity determining regions of antibody combining sites that make contact with antigen

E. A. Kabat, T. T. Wu, H. Bilofsky

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

From collected data on variable region sequences of heavy chains of immunoglobulins, the probability of random associations of any two amino acid residues in the complementarity determining segments was computed, and pairs of residues occurring significantly more frequently than expected were selected by computer. Significant associations between Phe 32 and Tyr 33, Phe 32 and Glu 35, and Tyr 33 and Glu 35 were found in six proteins, all of which were mouse myeloma proteins which bound phosphorylcholine (= phosphocholine). From the x ray structure of McPC603, Tyr 33 and Glu 35 are contacting residues; a seventh phosphorylcholine binding mouse myeloma protein also contained Phe 32 and Tyr 33 but position 35 had only been determined as Glx and thus this position had not been selected. Met 34 occurred in all seven phosphorylcholine binding myeloma proteins but was also present at this position in 29 other proteins and thus was not selected; it is seen in the x ray structure not to be a contacting residue. The role of Phe 32 is not obvious but it could have some conformational influence. A human phosphorylcholine binding myeloma protein also had Phe, Tyr, and Met at positions 32, 33, and 34, but had Asp instead of Glu at position 35 and showed a lower binding constant. The ability to use sequence data to locate residues in complementarity determining segments making contact with antigenic determinants and those playing essentially a structural role would contribute substantially to the understanding of antibody specificity.

Original languageEnglish (US)
Pages (from-to)617-619
Number of pages3
JournalProceedings of the National Academy of Sciences of the United States of America
Volume73
Issue number2
DOIs
StatePublished - 1976

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'Attempts to locate residues in complementarity determining regions of antibody combining sites that make contact with antigen'. Together they form a unique fingerprint.

Cite this