Investigating antibody specificity using computer graphics and protein engineering

Abstract Antibodies are a class of binding proteins whose genetic construction allows the expression of a vast repertoire of specificities. Our understanding of the molecular basis for this specificity stems largely from structural studies of antibodies to small, essentially rigid molecules, or haptens. Recent work on antibodies to larger, protein antigens has revealed some interesting new features, the molecular origins of which it is now possible to explore via protein engineering.

[1]  L M Amzel,et al.  Preliminary refinement and structural analysis of the Fab fragment from human immunoglobulin new at 2.0 A resolution. , 1981, The Journal of biological chemistry.

[2]  K. Karjalainen,et al.  An unusual type of V–J joining diversifies the primary repertoire of mouse λ1 light chains , 1985, Nature.

[3]  E. Padlan,et al.  Model-building studies of antigen-binding sites: the hapten-binding site of mopc-315. , 1977, Cold Spring Harbor symposia on quantitative biology.

[4]  A R Rees,et al.  Nucleotide sequences of five anti‐lysozyme monoclonal antibodies. , 1985, The EMBO journal.

[5]  A. Wilson,et al.  Mapping the antigenic epitope for a monoclonal antibody against lysozyme. , 1982, Journal of immunology.

[6]  E. Padlan,et al.  Structural basis for the specificity of phosphorylcholine-binding immunoglobulins. , 1976, Immunochemistry.

[7]  A. Colman,et al.  Synthesis and secretion of mouse immunoglobulin chains from Xenopus oocytes , 1981, Nature.

[8]  M Karplus,et al.  Molecular anatomy of the antibody binding site. , 1983, The Journal of biological chemistry.

[9]  R. Poljak,et al.  Three-dimensional structure of an antigen–antibody complex at 6 Å resolution , 1985, Nature.

[10]  C. Milstein,et al.  Somatic mutation and the maturation of immune response to 2-phenyl oxazolone , 1984, Nature.

[11]  Robert O. Fox,et al.  Recombinant antibodies possessing novel effector functions , 1984, Nature.

[12]  T. T. Wu,et al.  AN ANALYSIS OF THE SEQUENCES OF THE VARIABLE REGIONS OF BENCE JONES PROTEINS AND MYELOMA LIGHT CHAINS AND THEIR IMPLICATIONS FOR ANTIBODY COMPLEMENTARITY , 1970, The Journal of experimental medicine.

[13]  A. Rees,et al.  Modelling of the combining sites of three anti‐lysozyme monoclonal antibodies and of the complex between one of the antibodies and its epitope. , 1986, The EMBO journal.

[14]  G. Moore,et al.  Protein antigenicity, organization and mobility , 1985 .

[15]  A R Rees,et al.  Three distinct epitopes within the loop region of hen egg lysozyme defined with monoclonal antibodies. , 1985, The EMBO journal.

[16]  Arthur J. Olson,et al.  The reactivity of anti-peptide antibodies is a function of the atomic mobility of sites in a protein , 1984, Nature.

[17]  Leroy Hood,et al.  A single VH gene segment encodes the immune response to phosphorylcholine: Somatic mutation is correlated with the class of the antibody , 1981, Cell.

[18]  C. Milstein,et al.  mRNA sequences define an unusually restricted IgG response to 2-phenyloxazolone and its early diversification , 1983, Nature.