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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Proper implementation of the Drugs and Cosmetics Act of 1940, development of more elaborate guidelines on quality control aspects, and development of marker-based standards are needed to produce safe and effective herbal medicines in India. Because evidence-based studies are becoming increasingly essential for establishing the safety and efficacy of herbal products in the domestic and export market, more focus should be placed on scientific and technological advancement in the field of herbal medicine. Regulatory harmonization becomes essential to mitigate the delays in commercialization across countries.

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We demonstrate that the mitogen-activated protein kinases extracellular signal-regulated kinase (ERK)-1 and ERK-2 have a central role in mediating T-cell receptor-dependent induction of IL4 expression in human CD4+ T cells. Significantly, this involved a novel mechanism wherein receptor cross-linking induced activated ERK to physically associate with a promoter element on the IL4 gene. The proximally localized ERK then facilitated recruitment of the key transcription factors necessary for initiating IL4 gene transcription. Although both ERK-1 and ERK-2 bound to the promoter, recruitment of either one alone was found to be sufficient. We thus identify a novel mode of function for ERK wherein its physical association with the promoter serves as a prerequisite for enhanceosome assembly. This unusual pathway is also indispensable for human Th2-cell differentiation.