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Structural mechanism for affinity maturation of an anti-lysozyme antibody.

Cauerhff A, Goldbaum FA, Braden BC
Proc Natl Acad Sci U S A 101 3539-44 (2004)
Cited: 54 times
EuropePMC logo PMID: 14988501

Abstract

In the immune response against a typical T cell-dependent protein antigen, the affinity maturation process is fast and is associated with the early class switch from IgM to IgG. As such, a comprehension of the molecular basis of affinity maturation could be of great importance in biomedical and biotechnological applications. Affinity maturation of anti-protein antibodies has been reported to be the result of small structural changes, mostly confined to the periphery of the antigen-combining site. However, little is understood about how these small structural changes account for the increase in the affinity toward the antigen. Herein, we present the three-dimensional structure of the Fab fragment from BALB/c mouse mAb F10.6.6 in complex with the antigen lysozyme. This antibody was obtained from a long-term exposure to the antigen. mAb F10.6.6, and the previously described antibody D44.1, are the result of identical or nearly identical somatic recombination events. However, different mutations in the framework and variable regions result in an approximately 10(3) higher affinity for the F10.6.6 antibody. The comparison of the three-dimensional structures of these Fab-lysozyme complexes reveals that the affinity maturation produces a fine tuning of the complementarity of the antigen-combining site toward the epitope, explaining at the molecular level how the immune system is able to increase the affinity of an anti-protein antibody to subnanomolar levels.

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Related citations provided by authors (1)

  1. Lack of significant differences in association rates and affinities of antibodies from short-term and long-term responses to hen egg lysozyme. Goldbaum FA, Cauerhff A, Velikovsky CA, Llera AS, Riottot MM, Poljak RJ J. Immunol. 162 6040-6045 (1999)

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