Sequence, Structure, and Function Relationships of Human Antibodies

Abstract

The human adaptive immune system is mediated in part by B cells, which produce antibodies to protect the body from infection. Antibodies are protein molecules responsible for recognizing and binding pathogenic targets (i.e., antigens) to mediate effective neutralization of the microorganism. In recent years, emerging technologies such as next generation sequencing and computational structure prediction have had a substantial impact on studies of human antibodies. These technologies have improved our understanding of antibody sequence, structure and function relationships. The development of a broadly protective anti-influenza antibody response following vaccination was tracked over time using next generation sequencing. Knowledge-based restraints calculated from analysis of conserved structural motifs in antigen-binding antibody protein loops improved the accuracy of antibody structural predictions using the Rosetta software suite for macromolecular modeling. Combining these sequencing techniques with structure prediction allowed for the development of a novel method for structure-based discovery of functional antibodies from human donors.