high-resolution description of antibody heavy-chain repertoires in humans高分辨率的描述抗体重链在人类体验.pdfVIP

High-Resolution Description of Antibody Heavy-Chain Repertoires in Humans 1,2 ¤a 2¤b 2 2 2 2 Ramy Arnaout * , William Lee , Patrick Cahill , Tracey Honan , Todd Sparrow , Michael Weiand , Chad Nusbaum2, Klaus Rajewsky3., Sergei B. Koralov3.¤c 1 Department of Pathology, Brigham and Women’s Hospital, Boston, Massachusetts, United States of America, 2 Genome Sequencing and Analysis Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America, 3 Program in Cellular and Molecular Medicine, Children’s Hospital and Immune Disease Institute, Harvard Medical School, Boston, Massachusetts, United States of America Abstract Antibodies’ protective, pathological, and therapeutic properties result from their considerable diversity. This diversity is almost limitless in potential, but actual diversity is still poorly understood. Here we use deep sequencing to characterize the diversity of the heavy-chain CDR3 region, the most important contributor to antibody binding specificity, and the constituent V, D, and J segments that comprise it. We find that, during the stepwise D-J and then V-DJ recombination events, the choice of D and J segments exert some bias on each other; however, we find the choice of the V segment is essentially independent of both. V, D, and J segments are utilized with different frequencies, resulting in a highly skewed representation of VDJ combinations in the repertoire. Nevertheless, the pattern of segment usage was almost identical between two different individuals. The pattern of V, D, and J segment usage and recombination was insufficient to explain overlap that was observed bet