NDLI: Trade-offs in antibody repertoires to complex antigens

Content Provider	PubMed Central
Author	Childs, Lauren M. Baskerville, Edward B. Cobey, Sarah
Copyright Year	2015
Abstract	Pathogens vary in their antigenic complexity. While some pathogens such as measles present a few relatively invariant targets to the immune system, others such as malaria display considerable antigenic diversity. How the immune response copes in the presence of multiple antigens, and whether a trade-off exists between the breadth and efficacy of antibody (Ab)-mediated immune responses, are unsolved problems. We present a theoretical model of affinity maturation of B-cell receptors (BCRs) during a primary infection and examine how variation in the number of accessible antigenic sites alters the Ab repertoire. Naive B cells with randomly generated receptor sequences initiate the germinal centre (GC) reaction. The binding affinity of a BCR to an antigen is quantified via a genotype–phenotype map, based on a random energy landscape, that combines local and distant interactions between residues. In the presence of numerous antigens or epitopes, B-cell clones with different specificities compete for stimulation during rounds of mutation within GCs. We find that the availability of many epitopes reduces the affinity and relative breadth of the Ab repertoire. Despite the stochasticity of somatic hypermutation, patterns of immunodominance are strongly shaped by chance selection of naive B cells with specificities for particular epitopes. Our model provides a mechanistic basis for the diversity of Ab repertoires and the evolutionary advantage of antigenically complex pathogens.
Related Links	http://dx.doi.org/10.1098/rstb.2014.0245
Starting Page	20140245
File Format	PDF
ISSN	09628436
e-ISSN	14712970
Journal	Philosophical Transactions of the Royal Society B: Biological Sciences
Issue Number	1676
Volume Number	370
Language	English
Publisher	The Royal Society
Publisher Date	2015-09-05
Access Restriction	Open
Rights Holder	The Royal Society
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Biochemistry, Genetics and Molecular Biology Agricultural and Biological Sciences

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