Title: Enhancement and destruction of antibody function by somatic mutation: unequal occurrence is controlled by V gene combinatorial associations.
Abstract: Research Article15 June 1995free access Enhancement and destruction of antibody function by somatic mutation: unequal occurrence is controlled by V gene combinatorial associations. C. Chen C. Chen Department of Microbiology and Immunology, Oregon Health Sciences University, Portland 97201, USA. Search for more papers by this author V.A. Roberts V.A. Roberts Department of Microbiology and Immunology, Oregon Health Sciences University, Portland 97201, USA. Search for more papers by this author S. Stevens S. Stevens Department of Microbiology and Immunology, Oregon Health Sciences University, Portland 97201, USA. Search for more papers by this author M. Brown M. Brown Department of Microbiology and Immunology, Oregon Health Sciences University, Portland 97201, USA. Search for more papers by this author M.P. Stenzel-Poore M.P. Stenzel-Poore Department of Microbiology and Immunology, Oregon Health Sciences University, Portland 97201, USA. Search for more papers by this author M.B. Rittenberg M.B. Rittenberg Department of Microbiology and Immunology, Oregon Health Sciences University, Portland 97201, USA. Search for more papers by this author C. Chen C. Chen Department of Microbiology and Immunology, Oregon Health Sciences University, Portland 97201, USA. Search for more papers by this author V.A. Roberts V.A. Roberts Department of Microbiology and Immunology, Oregon Health Sciences University, Portland 97201, USA. Search for more papers by this author S. Stevens S. Stevens Department of Microbiology and Immunology, Oregon Health Sciences University, Portland 97201, USA. Search for more papers by this author M. Brown M. Brown Department of Microbiology and Immunology, Oregon Health Sciences University, Portland 97201, USA. Search for more papers by this author M.P. Stenzel-Poore M.P. Stenzel-Poore Department of Microbiology and Immunology, Oregon Health Sciences University, Portland 97201, USA. Search for more papers by this author M.B. Rittenberg M.B. Rittenberg Department of Microbiology and Immunology, Oregon Health Sciences University, Portland 97201, USA. Search for more papers by this author Author Information C. Chen1, V.A. Roberts1, S. Stevens1, M. Brown1, M.P. Stenzel-Poore1 and M.B. Rittenberg1 1Department of Microbiology and Immunology, Oregon Health Sciences University, Portland 97201, USA. The EMBO Journal (1995)14:2784-2794https://doi.org/10.1002/j.1460-2075.1995.tb07278.x PDFDownload PDF of article text and main figures. ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinked InMendeleyWechatReddit Figures & Info We examined the positive and negative effects of somatic mutation on antibody function using saturation mutagenesis in vitro to mimic the potential of the in vivo process to diversify antibodies. Identical mutations were introduced into the second complementarity determining region of two anti-phosphocholine antibodies, T15 and D16, which share the same germline VH gene sequence. T15 predominates in primary responses and does not undergo affinity maturation. D16 is representative of antibodies that co-dominate in memory responses and do undergo affinity maturation. We previously reported that > 50% of T15 mutants had decreased antigen binding capacity. To test if this high frequency of binding loss was unique to T15 or a consequence of random point mutations applicable to other combining sites, we analyzed the same mutations in D16. We show that D16 suffers a similar loss of function, indicating an equally high potential for B-cell wastage. However, only D16 displayed the capacity for somatic mutation to improve antigen binding, which should enhance its persistence in memory responses. Mutation of residues contacting the haptenic group, as determined by molecular modeling, did not improve binding. Instead, productive mutations occurred in residues that either contacted carrier protein or were distant from the antigen binding site, possibly increasing binding site flexibility through long-range effects. Targeting such residues for mutation should aid in the rational design of improved antibodies. Previous ArticleNext Article Volume 14Issue 121 June 1995In this issue RelatedDetailsLoading ...