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Immunity. 2000 Nov;13(5):611-20.

Maturation of an antibody response is governed by modulations in flexibility of the antigen-combining site.

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Immunology Group International Centre for Genetic Engineering and Biotechnology Aruna Asaf Ali Marg 110 067, New Delhi, India.


Although affinity maturation constitutes an integral part of T-dependent humoral responses, its structural basis is less well understood. We compared the physicochemical properties of antigen binding of several independent antibody panels derived from both germline and secondary responses. We found that antibody maturation essentially reflects modulations in entropy-control of the association, but not dissociation, step of the binding. This influence stems from variations in conformational heterogeneity of the antigen-combining site, which in turn regulates both the affinity and specificity for antigen. Thus, the simple device of manipulating conformational flexibility of paratope provides a mechanism wherein the transition from a degenerate recognition capability to a high-fidelity effector response is readily achieved, with the minimum of somatic mutations.

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