Affinity maturation

Daugherty, P.S., Chen, G., Iverson, B.L. and Georgiou, G. (2000) Quantitative analysis of the effect of the mutation frequency on the affinity maturation of single chainFv antibodies. Proceedings of the National Academy of Sciences of the United States of America, 97, 2029-2034. 

Chong, L.T. Duan, Y. Wang, L. Massova, I. Kollman, P., Molecular dynamics and free energy calculations applied to affinity maturation in antibody 48G7, Proc. Natl Acad. Sci. USA 1999, 96, 14330-14335... 

Scaffolds with functional residues Affinity maturation Engineering avidity valency Tailoring effector functions... 

Affinity maturation of antibodies has been achieved by the introduction of diversity into the V-genes, which then creates diversity within the antigen binding sites. This secondary library is then subjected to a selection that will enrich high affinity variants. More or less random diversity may be introduced by altering variable domain pairings in a process called... 

Hawkins, R. E., Russell, S. J., and Winter, G. (1992) Selection of phage antibodies by binding affinity mimicking affinity maturation J Mol Biol. 226, 889-896. 

Gram, H., Marconi, LA, Barbas, C. F., Ill, Collet, T. A., Lemer, R. A, and Kang, A. S (1992) In vitro selection and affinity maturation of antibodies from a naive combinatorial immunoglobulin library. Proc Natl Acad Sci USA 89,3576-3580... 

Antibody affinity. The affinity of the antibodies is much greater in the secondary response as opposed to the primary response, which is termed affinity maturation. ... 

Allen, D., Simon, T., Sablitzky, F., Rajewsky, K., Cumano, A. (1988). Antibody engineering for the analysis of affinity maturation of an anti-hapten response. EMBO J. 7, 1995-2001. 

Eisen, H.N. (1989). Affinity maturation a retrospective view. In Molecular evolution on rugged landscapes proteins, RNA and the immune system (Perelson, A.S. Kauffman, A.A., Eds.), pp. 75-82. Addison Wesley, Redwood City. 

Wilson, M., Hsu, E., Marcuz, A., Courtet, M., Du Pasquier, L., Steinberg, C. (1992). What limits affinity maturation in Xenopus—the rate of somatic mutation or the ability to select mutants EMBOJ. 11,4337-4347. 

Remaining B-lymphocytes in the bone marrow have the potential to respond to an enormous number of foreign substances (antigens). Once exposed to antigens, the cells, which have the best fit antibody to the target, undergo clonal expansion to increase the cell numbers and affinity maturation to increase the specificity (fit) of the antibody molecules produced. 

Harvey, B. R., Rogers, G. K., Iverson, B. I., and Georgiou, G. (2002) Anchored periplasmic expression (APEx) a new platform for library screening and affinity maturation. Conference book IBC s 13th international conference, Antibody Engineering. 

Anti-dsDNA Antibodies Are Antigen-Driven. There is evidence that variable regions of both heavy and light chains of both murine and human monoclonal anti-dsDNA antibodies are produced after an affinity maturation process via isotype switching, clonal selection, and somatic mutation (D5, D9, Wll, C16, V3). These findings suggest that anti-dsDNA antibodies are produced by an... 

Macken and Perelson studied antibody affinity maturation as a random walk on the random energy landscape (Macken and Perelson, 1989 Macken et al., 1991 Macken and Perelson, 1991). The total number of mutants tried before a positive mutation is discovered T(F) is a measure of the change in the necessary size of the mutant library. The expected value of T, given that F is not a local optimum, is derived as... 

STRUCTURAL ANALYSIS OF AFFINITY MATURED ANTIBODIES AND LABORATORY-EVOLVED ENZYMES... 

Over half of the structurally characterized catalytic antibodies are from the esterolytic class of reactivity. This discussion will focus on 48G7, the most exemplary antibody from this class. In this antibody, the bound and free forms of both germline and mature antibodies have been structurally characterized, allowing for the first structural analysis of the affinity maturation process in a catalytic antibody system (Patten et al., 1996 Wedemayer et al., 1997a Wedemayer et al., 1997b). 

Fig. 9. (a) Overlay of the combining site for AZ-28 affinity-matured structures, with... 

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