{"doi":"10.4049/jimmunol.2100141","title":"Cutting Edge: TCR-β Selection Is Required at the CD4+CD8+ Stage of Human T Cell Development","abstract":"Abstract T cell development is predicated on the successful rearrangement of the TCR gene loci, which encode for Ag-specific receptors. Recombination-activating gene (RAG) 2 is required for TCR gene rearrangements, which occur during specific stages of T cell development. In this study, we differentiated human pluripotent stem cells with a CRISPR/Cas9-directed deletion of the RAG2 gene (RAG2-KO) to elucidate the requirement for the TCR β-chain in mediating β-selection during human T cell development. In stark contrast to mice, human RAG2-KO T lineage progenitors progressed to the CD4+CD8+ double-positive (DP) stage in the absence of TCRβ rearrangements. Nonetheless, RAG2-KO DPs retrovirally transduced to express a rearranged TCR β-chain showed increased survival and proliferation as compared with control-transduced RAG2-KO DPs. Furthermore, transcriptomic analysis showed that TCRβ- and control-transduced RAG2-KO DPs differed in gene pathways related to survival and proliferation. Our results provide important insights as to the distinct requirement for the TCR β-chain during human T cell development.","journal":"The Journal of Immunology","year":2021,"id":199996,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9548,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":639054,"name":"Patrick M. Brauer","orcid":"0000-0001-7788-5204","position":1,"is_corresponding":false},{"id":777673,"name":"Elisa C Martinez","orcid":null,"position":2,"is_corresponding":false},{"id":430568,"name":"Xiaotian Huang","orcid":"0000-0003-1145-8386","position":3,"is_corresponding":false},{"id":777079,"name":"Ning Yu","orcid":"0000-0003-2812-9300","position":4,"is_corresponding":false},{"id":430570,"name":"Michele K. Anderson","orcid":"0000-0002-8820-5910","position":5,"is_corresponding":false},{"id":430572,"name":"Yang Li","orcid":"0000-0002-8805-4980","position":6,"is_corresponding":false},{"id":378627,"name":"Juan Carlos Zúñiga‐Pflücker","orcid":"0000-0003-2538-3178","position":7,"is_corresponding":false},{"id":488523,"name":"Edward L.Y. Chen","orcid":"0000-0001-7197-2243","position":0,"is_corresponding":true}],"reference_count":35,"raw_metadata":null,"created_at":"2026-07-18T23:50:44.479665Z","pmid":"33941655","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":[]}