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ABSTRACT The main function of the immune system in health is to protect the host from infection by microbes and parasites. Because immune responses to nonself bear the risk of unleashing

accidental immunity against self, evolution has endowed the immune system with central and peripheral mechanisms of tolerance, including regulatory T and B cells. Although the past two

decades have witnessed the successful clinical translation of a whole host of novel therapies for the treatment of chronic inflammation, the development of antigen-based approaches capable

of selectively blunting autoimmune inflammation without impairing normal immunity has remained elusive. Earlier autoantigen-specific approaches employing peptides or whole antigens have

evolved into strategies that seek to preferentially deliver these molecules to autoreactive T cells either indirectly, via antigen-presenting cells, or directly, via major histocompatibility

complex molecules, in ways intended to promote clonal deletion and/or immunoregulation. The disease specificity, mechanistic underpinnings, developability and translational potential of

many of these strategies remain unclear. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through

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support SIMILAR CONTENT BEING VIEWED BY OTHERS ANTIGEN-SPECIFIC IMMUNOTHERAPIES FOR AUTOIMMUNE DISEASE Article 16 December 2024 SEQUENTIAL IMMUNOTHERAPY: TOWARDS CURES FOR AUTOIMMUNITY

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inflammatory arthritis. _Ann. Rheum. Dis._ 76, 227–234 (2017). Article  CAS  PubMed  Google Scholar  Download references ACKNOWLEDGEMENTS We thank the members of our laboratories for their

contributions and insights. The authors’ work summarized here was funded by the Canadian Institutes of Health Research (CIHR), Diabetes Canada, the Crohn’s and Colitis Foundation of Canada,

the Multiple Sclerosis Society of Canada (MSSC), ISCIII and FEDER (PIE14/00027, PI15/0797), NEURON-ERANET (European Research Projects on Neuroinflammation; NEURON7-FP-715-018), the

Ministerio de Economia y Competitividad of Spain (MINECO) and Generalitat de Catalunya (SGR and CERCA Programmes). P. Serra was an investigator of the Ramon y Cajal Re-integration Program

and is supported by a JDRF Career Development Award. P. Santamaria was a Scientist of the Alberta-Innovates – Health Solutions (AI–HS) and a scholar of the Instituto de Investigaciones

Sanitarias Carlos III. The JMDRC was supported by the Diabetes Association (Foothills) and currently by Diabetes Canada. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Institut

D’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain Pau Serra & Pere Santamaria * Julia McFarlane Diabetes Research Centre (JMDRC) and Department of Microbiology,

Immunology and Infectious Diseases, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada Pere Santamaria Authors * Pau Serra

View author publications You can also search for this author inPubMed Google Scholar * Pere Santamaria View author publications You can also search for this author inPubMed Google Scholar

CORRESPONDING AUTHORS Correspondence to Pau Serra or Pere Santamaria. ETHICS DECLARATIONS COMPETING INTERESTS P. Santamaria is scientific founder of Parvus Therapeutics Inc. and has a

financial interest in the company. ADDITIONAL INFORMATION PUBLISHER’S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional

affiliations. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Serra, P., Santamaria, P. Antigen-specific therapeutic approaches for autoimmunity. _Nat

Biotechnol_ 37, 238–251 (2019). https://doi.org/10.1038/s41587-019-0015-4 Download citation * Received: 01 May 2018 * Accepted: 04 January 2019 * Published: 25 February 2019 * Issue Date:

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