Could cross‐reactivity rescue Foxp3+ regulatory T cell precursors from thymic deletion?
Thymocytes that bind with high affinity to peptides displayed by MHC class II (pMHC‐II) are deleted while low‐affinity binders differentiate into naive CD4+ T cells. However, Foxp3+ regulatory T cells (Tregs) seem to defy this binary choice as their precursors require high‐affinity interaction with...
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| Veröffentlicht in: | Scandinavian journal of immunology 2021-01, Vol.93 (1), p.e12940-n/a |
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| container_title | Scandinavian journal of immunology |
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| creator | Usharauli, David Kamala, Tirumalai |
| description | Thymocytes that bind with high affinity to peptides displayed by MHC class II (pMHC‐II) are deleted while low‐affinity binders differentiate into naive CD4+ T cells. However, Foxp3+ regulatory T cells (Tregs) seem to defy this binary choice as their precursors require high‐affinity interaction with pMHC‐II for maturation in the thymus. Here, we rely on the antigen‐specific interpretive framework, SPIRAL (Specific ImmunoRegulatory Algorithm), to propose that Tregs escape thymic deletion by forming dyads with IL‐2‐producing T cells via antigen cross‐reactivity. This interpretation reconciles contradictions related to Treg ontogeny in the thymus and their role in modulating antigen‐specific immune responses. |
| doi_str_mv | 10.1111/sji.12940 |
| format | Article |
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Kamala, Tirumalai</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3880-9327dfff6fb27e12e36e3633035a96e8c127c46f7af011fdcbc1aba403e0b1823</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Affinity</topic><topic>Animals</topic><topic>Antigens</topic><topic>CD4 antigen</topic><topic>Cell differentiation</topic><topic>Clonal deletion</topic><topic>Clonal Evolution</topic><topic>Clonal Selection, Antigen-Mediated</topic><topic>Cross Reactions - immunology</topic><topic>cross‐reactivity</topic><topic>Forkhead Transcription Factors - metabolism</topic><topic>Foxp3</topic><topic>Foxp3 protein</topic><topic>Humans</topic><topic>IL‐2</topic><topic>Immunoregulation</topic><topic>Lymphocyte Activation</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Major histocompatibility complex</topic><topic>microbiota</topic><topic>Ontogeny</topic><topic>T regs</topic><topic>T-Cell Antigen Receptor Specificity</topic><topic>T-Lymphocyte Subsets - immunology</topic><topic>T-Lymphocyte Subsets - metabolism</topic><topic>T-Lymphocytes, Regulatory - immunology</topic><topic>T-Lymphocytes, Regulatory - metabolism</topic><topic>Thymocytes</topic><topic>Thymus</topic><topic>Thymus gland</topic><topic>Thymus Gland - immunology</topic><topic>Thymus Gland - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Usharauli, David</creatorcontrib><creatorcontrib>Kamala, Tirumalai</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Scandinavian journal of immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Usharauli, David</au><au>Kamala, Tirumalai</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Could cross‐reactivity rescue Foxp3+ regulatory T cell precursors from thymic deletion?</atitle><jtitle>Scandinavian journal of immunology</jtitle><addtitle>Scand J Immunol</addtitle><date>2021-01</date><risdate>2021</risdate><volume>93</volume><issue>1</issue><spage>e12940</spage><epage>n/a</epage><pages>e12940-n/a</pages><issn>0300-9475</issn><eissn>1365-3083</eissn><abstract>Thymocytes that bind with high affinity to peptides displayed by MHC class II (pMHC‐II) are deleted while low‐affinity binders differentiate into naive CD4+ T cells. However, Foxp3+ regulatory T cells (Tregs) seem to defy this binary choice as their precursors require high‐affinity interaction with pMHC‐II for maturation in the thymus. Here, we rely on the antigen‐specific interpretive framework, SPIRAL (Specific ImmunoRegulatory Algorithm), to propose that Tregs escape thymic deletion by forming dyads with IL‐2‐producing T cells via antigen cross‐reactivity. This interpretation reconciles contradictions related to Treg ontogeny in the thymus and their role in modulating antigen‐specific immune responses.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>32776320</pmid><doi>10.1111/sji.12940</doi><tpages>5</tpages><orcidid>https://orcid.org/0000-0001-6340-8597</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Affinity Animals Antigens CD4 antigen Cell differentiation Clonal deletion Clonal Evolution Clonal Selection, Antigen-Mediated Cross Reactions - immunology cross‐reactivity Forkhead Transcription Factors - metabolism Foxp3 Foxp3 protein Humans IL‐2 Immunoregulation Lymphocyte Activation Lymphocytes Lymphocytes T Major histocompatibility complex microbiota Ontogeny T regs T-Cell Antigen Receptor Specificity T-Lymphocyte Subsets - immunology T-Lymphocyte Subsets - metabolism T-Lymphocytes, Regulatory - immunology T-Lymphocytes, Regulatory - metabolism Thymocytes Thymus Thymus gland Thymus Gland - immunology Thymus Gland - metabolism |
| title | Could cross‐reactivity rescue Foxp3+ regulatory T cell precursors from thymic deletion? |
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