There are many obstacles to achieve this, perhaps most importantly in the initial selection of antibodies that bind to a specific antigen of interest-improvements in structural modeling, docking, and binding affinity prediction in particular will help this.Įven though there is a large quantity of data already available, there is a vast amount of the antibody sequence space that remains unknown. Although it is too soon to say whether an entirely in silico protocol would produce better results than an experimental one, it would remove the need for expensive and time-consuming experimental work and would mean the immunization of animals is no longer required. Consolidating all of the knowledge gained from large-scale repertoire analysis may enable the creation of an in silico immune system, or at the least a completely human-like synthetic repertoire that can be screened to identify potential therapeutics. In the long term, however, the objective of many researchers is to make the discovery of new therapeutic antibodies completely computational, with little or no human input. For example, after a potential binder is identified experimentally, clonotyping can be used to select similar antibodies from a repertoire, thereby expanding the pool of candidates for further study. Biological insights from antibody repertoire dataĬurrently, it is possible for the computational approaches such as those described in this review to be used in tandem with experimental work. We give examples of how this data has been used to give insights into the workings of the immune system, look at how it can be enhanced with structural information, explore how it offers new avenues for therapeutic antibody discovery and development, and consider what advances may be made in the future. In this review, we explore what can be done with the wealth of antibody sequence data stored in repositories such as OAS. data sets in OAS contain between 20,000 and 300 million redundant sequences) and most studies feature only the heavy chain or have no pairing information, the data available still provides opportunities to investigate many different aspects of the immune response. Although the snapshots of the repertoire achieved through sequencing are actually small relative to the potential number of antibodies present in an organism ( e.g. HIV, hepatitis B, flu, etc.), and in some cases, OAS has the repertoires of the same individual both pre- and post-immunization. Repertoires from vaccination studies also feature ( e.g. repertoires from individuals who have been exposed to a specific antigen) as well as healthy ones (meaning the individual has not been exposed to the antigen of interest and also has not suffered from a disorder of the immune system). Sequences are available for six different species, with the majority (64%) being human. The studies included in OAS cover many different repertoire characteristics. We also consider how structural information can be used to enhance these data and may lead to more accurate depictions of the sequence space and to applications in the discovery of new therapeutics. We highlight its utility for providing insights into how the naive immune repertoire is generated and how it responds to antigens. In this review, we discuss the many ways in which BCR repertoire data have been or could be exploited. This wealth of data has created opportunities to learn more about our immune system. antigen-inexperienced) and that after immunization.
Repertoires are available that represent both the naive state ( i.e. The Observed Antibody Space database, for example, currently contains over a billion sequences from 68 different studies. Next-generation sequencing technologies are being increasingly used to query the antibody, or B-cell receptor (BCR), sequence repertoire, and the amount of BCR data in public repositories is growing. The antibodies present in an organism therefore report on its immune status, describe its innate ability to deal with harmful substances, and reveal how it has previously responded. In an organism, after antigen exposure, antibodies specific to that antigen are enriched through clonal selection, expansion, and somatic hypermutation. Because they can be developed to bind to many disease agents, antibodies can be used as therapeutics. Mammals can efficiently create vast numbers of antibodies with different sequences capable of binding to any antigen with high affinity and specificity. Glycobiology and Extracellular MatricesĪntibodies are vital proteins of the immune system that recognize potentially harmful molecules and initiate their removal.
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