{"doi":"10.1073/pnas.2003170117","title":"MHC-II alleles shape the CDR3 repertoires of conventional and regulatory naïve CD4\n                    <sup>+</sup>\n                    T cells","abstract":"<jats:p>\n                    T cell maturation and activation depend upon T cell receptor (TCR) interactions with a wide variety of antigenic peptides displayed in a given major histocompatibility complex (MHC) context. Complementarity-determining region 3 (CDR3) is the most variable part of the TCRα and -β chains, which govern interactions with peptide–MHC complexes. However, it remains unclear how the CDR3 landscape is shaped by individual MHC context during thymic selection of naïve T cells. We established two mouse strains carrying distinct allelic variants of\n                    <jats:italic>H2-A</jats:italic>\n                    and analyzed thymic and peripheral production and TCR repertoires of naïve conventional CD4\n                    <jats:sup>+</jats:sup>\n                    T (T\n                    <jats:sub>conv</jats:sub>\n                    ) and naïve regulatory CD4\n                    <jats:sup>+</jats:sup>\n                    T (T\n                    <jats:sub>reg</jats:sub>\n                    ) cells. Compared with tuberculosis-resistant C57BL/6 (H2-A\n                    <jats:sup>b</jats:sup>\n                    ) mice, the tuberculosis-susceptible H2-A\n                    <jats:sup>j</jats:sup>\n                    mice had fewer CD4\n                    <jats:sup>+</jats:sup>\n                    T cells of both subsets in the thymus. In the periphery, this deficiency was only apparent for T\n                    <jats:sub>conv</jats:sub>\n                    and was compensated for by peripheral reconstitution for T\n                    <jats:sub>reg</jats:sub>\n                    . We show that H2-A\n                    <jats:sup>j</jats:sup>\n                    favors selection of a narrower and more convergent repertoire with more hydrophobic and strongly interacting amino acid residues in the middle of CDR3α and CDR3β, suggesting more stringent selection against a narrower peptide–MHC-II context. H2-A\n                    <jats:sup>j</jats:sup>\n                    and H2-A\n                    <jats:sup>b</jats:sup>\n                    mice have prominent reciprocal differences in CDR3α and CDR3β features, probably reflecting distinct modes of TCR fitting to MHC-II variants. These data reveal the mechanics and extent of how MHC-II shapes the naïve CD4\n                    <jats:sup>+</jats:sup>\n                    T cell CDR3 landscape, which essentially defines adaptive response to infections and self-antigens.\n                  </jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2020,"id":677774,"datarank":0.611630616585858,"base_score":4.07753744390572,"endowment":4.07753744390572,"self_citation_contribution":0.611630616585858,"citation_network_contribution":0.0,"self_endowment_contribution":0.611630616585858,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":58,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1770904,"name":"Valeriia V. Kriukova","orcid":null,"position":1,"is_corresponding":false},{"id":1259222,"name":"Pavel V. Shelyakin","orcid":"0000-0003-0120-9319","position":2,"is_corresponding":false},{"id":1770905,"name":"Evgeny S. Egorov","orcid":"0000-0002-6495-7173","position":3,"is_corresponding":false},{"id":1770906,"name":"Alina Pereverzeva","orcid":null,"position":4,"is_corresponding":false},{"id":393387,"name":"Nina G. Bozhanova","orcid":"0000-0002-2164-5698","position":5,"is_corresponding":false},{"id":645146,"name":"Mikhail Shugay","orcid":"0000-0001-7826-7942","position":6,"is_corresponding":false},{"id":1770908,"name":"Dmitrii S. Shcherbinin","orcid":null,"position":7,"is_corresponding":false},{"id":618933,"name":"Mikhail V. Pogorelyy","orcid":"0000-0003-0773-1204","position":8,"is_corresponding":false},{"id":1770910,"name":"Ekaterina M. Merzlyak","orcid":null,"position":9,"is_corresponding":false},{"id":1770913,"name":"Vasiliy N. Zubov","orcid":null,"position":10,"is_corresponding":false},{"id":36757,"name":"Jens Meiler","orcid":"0000-0001-8945-193X","position":11,"is_corresponding":false},{"id":269954,"name":"Dmitriy M. Chudakov","orcid":"0000-0003-0430-790X","position":12,"is_corresponding":false},{"id":495739,"name":"Alexander Apt","orcid":"0000-0002-3683-3085","position":13,"is_corresponding":false},{"id":1000416,"name":"Olga V. Britanova","orcid":"0000-0002-6295-1392","position":14,"is_corresponding":false},{"id":1770903,"name":"Nadezhda N. Logunova","orcid":"0000-0001-7086-6158","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"MHC-II alleles shape the CDR3 repertoires of conventional and regulatory naïve CD4\n                    <sup>+</sup>\n                    T cells","abstract":"<jats:p>\n                    T cell maturation and activation depend upon T cell receptor (TCR) interactions with a wide variety of antigenic peptides displayed in a given major histocompatibility complex (MHC) context. Complementarity-determining region 3 (CDR3) is the most variable part of the TCRα and -β chains, which govern interactions with peptide–MHC complexes. However, it remains unclear how the CDR3 landscape is shaped by individual MHC context during thymic selection of naïve T cells. We established two mouse strains carrying distinct allelic variants of\n                    <jats:italic>H2-A</jats:italic>\n                    and analyzed thymic and peripheral production and TCR repertoires of naïve conventional CD4\n                    <jats:sup>+</jats:sup>\n                    T (T\n                    <jats:sub>conv</jats:sub>\n                    ) and naïve regulatory CD4\n                    <jats:sup>+</jats:sup>\n                    T (T\n                    <jats:sub>reg</jats:sub>\n                    ) cells. Compared with tuberculosis-resistant C57BL/6 (H2-A\n                    <jats:sup>b</jats:sup>\n                    ) mice, the tuberculosis-susceptible H2-A\n                    <jats:sup>j</jats:sup>\n                    mice had fewer CD4\n                    <jats:sup>+</jats:sup>\n                    T cells of both subsets in the thymus. In the periphery, this deficiency was only apparent for T\n                    <jats:sub>conv</jats:sub>\n                    and was compensated for by peripheral reconstitution for T\n                    <jats:sub>reg</jats:sub>\n                    . We show that H2-A\n                    <jats:sup>j</jats:sup>\n                    favors selection of a narrower and more convergent repertoire with more hydrophobic and strongly interacting amino acid residues in the middle of CDR3α and CDR3β, suggesting more stringent selection against a narrower peptide–MHC-II context. H2-A\n                    <jats:sup>j</jats:sup>\n                    and H2-A\n                    <jats:sup>b</jats:sup>\n                    mice have prominent reciprocal differences in CDR3α and CDR3β features, probably reflecting distinct modes of TCR fitting to MHC-II variants. These data reveal the mechanics and extent of how MHC-II shapes the naïve CD4\n                    <jats:sup>+</jats:sup>\n                    T cell CDR3 landscape, which essentially defines adaptive response to infections and self-antigens.\n                  </jats:p>","is_dataset_classified":null,"base_score":4.07753744390572,"endowment":4.07753744390572,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"32482872","pmcid":"PMC7306996","openalex_id":"https://openalex.org/W3032559793","authors":[],"funders":[{"funder_name":"Russian Science Foundation","grant_id":"16-15-00149","title":null},{"funder_name":"Russian Foundation for Basic Research","grant_id":"19-015-00082","title":null}],"total_grants":2,"fwci":2.2463,"citation_percentile":0.89097241,"influential_citations":0,"citation_trend":[{"year":2019,"count":1},{"year":2020,"count":3},{"year":2021,"count":5},{"year":2022,"count":8},{"year":2023,"count":12},{"year":2024,"count":9},{"year":2025,"count":17},{"year":2026,"count":3}],"oa_status":"green","license":"https://www.pnas.org/site/aboutpnas/licenses.xhtml","oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/7306996","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/7306996","host_type":"repository"},{"url":"http://www.pnas.org/syndication/doi/10.1073/pnas.2003170117","host_type":"publisher"},{"url":"https://pnas.org/doi/pdf/10.1073/pnas.2003170117","host_type":"publisher"},{"url":"https://doi.org/10.1073/pnas.2003170117","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/32482872","host_type":"repository"}],"fields_of_study":["T-cell and B-cell Immunology","Immune Cell Function and Interaction","Immunotherapy and Immune Responses"],"mesh_terms":["Alleles","Animals","Histocompatibility Antigens Class II","Humans","Mice, Inbred C57BL","Receptors, Antigen, T-Cell","Spleen","Tuberculosis","CD4-Positive T-Lymphocytes","Complementarity Determining Regions","T-Lymphocytes, Regulatory","Mice"],"keywords":["Allele","Genetics","Major histocompatibility complex","Molecular biology","Biology","Gene","MHC-II","Regulatory T cells","Naïve Cd4+ T Cells","Tcr Repertoire Landscape"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"bioproject"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-17T04:32:11.884933Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}