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CD23 dependent epitope spreading

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a | Antigen X, recognized by a B-cell receptor (BCR) specific for epitope 1, is internalized, processed and presented by MHC class II molecules. T cells specific for antigen X1 participate in cognate interactions with the B cell, leading to the production of IgG antibodies specific for epitope X1, and, if followed by class-switch recombination (CSR), IgE antibodies. T cells generated in this initial process, specific for other peptide fragments (X2-specific T cells), may take part in cognate interactions with B cells specific for other epitopes (X2-specific B cells), leading to IgG and perhaps also IgE specific for epitope X2. Thus, B cells acting as antigen-presenting cells (APCs) using surface immunoglobulin 'spread' the response from one epitope to another, but only within the same antigen. b | By contrast, if the B cell that is activated by antigen expresses membrane CD23, it can internalize IgE bound to an allergen (Y) that is unrelated to antigen X and the specificity of that B cell. The figure shows a cognate interaction that leads to IgG and IgE specific for epitope X2 (as in part a), but the CD23-mediated internalization of allergen Y, to which a low titre of specific IgE antibodies must initially exist, leads to the production of allergen-Y-specific IgG and then IgE antibodies. The response thus spreads from antigen X to the unrelated allergen Y. Internalization of other allergen–IgE complexes by CD23 can further spread the response, just as 'professional' APCs bearing Fc receptors for IgG (FcgammaRs) simultaneously process unrelated antigens and spread IgG responses from one antigen to another. CD23-mediated antigen presentation is more efficient than surface-immunoglobulin-mediated antigen presentation, and therefore can enhance a low level response to an allergen (such as allergen Y) and promote spreading to other allergens. This epitope spreading from one allergen to another may explain how certain allergic subjects deteriorate from sensitivity to only one allergen to multiple sensitivities70.
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