A germline knowledge based computational approach for determining antibody complementarity determining regions

Molecular Immunology
Shanrong Zhao, Jin Lu

Abstract

Determination of framework regions (FRs) and complementarity determining regions (CDRs) in an antibody is essential for understanding the underlying biology as well as antibody engineering and optimization. However, there are no computational algorithms available to delimit an antibody sequence or a library of sequences into FRs and CDRs in a coherent and automatic fashion. Based upon the mapping relationships among mature antibody sequences and their corresponding germline gene segments, a novel computational algorithm has been developed for automatic determination of CDRs. Even though a human can make more than 10(12) different antibody molecules in its preimmune repertoire to fight off invading pathogens, these antibodies are generated from rearrangements of a very limited number of germline variable (V) gene, diversity (D) gene and joining (J) gene segments followed by somatic hypermutation. The framework regions FR1, FR2 and FR3 in mature antibodies are encoded by germline V gene segments, while FR4 is encoded by J gene segments. Since there are only a limited number of germline gene segments, these genes can be pre-delimited to generate a knowledge base of FRs and CDRs. Then for a given antibody sequence, the algorithm sc...Continue Reading

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