Automated identification of complementarity determining regions (CDRs) reveals peculiar characteristics of CDRs and B cell epitopes

Yanay Ofran, Avner Schlessinger, Burkhard Rost

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

Abstract

Exact identification of complementarity determining regions (CDRs) is crucial for understanding and manipulating antigenic interactions. One way to do this is by marking residues on the antibody that interact with B cell epitopes on the antigen. This, of course, requires identification of B cell epitopes, which could be done by marking residues on the antigen that bind to CDRs, thus requiring identification of CDRs. To circumvent this vicious circle, existing tools for identifying CDRs are based on sequence analysis or general biophysical principles. Often, these tools, which are based on partial data, fail to agree on the boundaries of the CDRs. Herein we present an automated procedure for identifying CDRs and B cell epitopes using consensus structural regions that interact with the antigens in all known antibody-protein complexes. Consequently, we provide the first comprehensive analysis of all CDR-epitope complexes of known three-dimensional structure. The CDRs we identify only partially overlap with the regions suggested by existing methods. We found that the general physicochemical properties of both CDRs and B cell epitopes are rather peculiar. In particular, only four amino acids account for most of the sequence of CDRs, and several types of amino acids almost never appear in them. The secondary structure content and the conservation of B cell epitopes are found to be different than previously thought. These characteristics of CDRs and epitopes may be instrumental in choosing which residues to mutate in experimental search for epitopes. They may also assist in computational design of antibodies and in predicting B cell epitopes.

Original languageEnglish
Pages (from-to)6230-6235
Number of pages6
JournalJournal of Immunology
Volume181
Issue number9
DOIs
StatePublished - 1 Nov 2008
Externally publishedYes

Fingerprint

Dive into the research topics of 'Automated identification of complementarity determining regions (CDRs) reveals peculiar characteristics of CDRs and B cell epitopes'. Together they form a unique fingerprint.

Cite this