{"doi":"10.1083/jcb.202205118","title":"Hyperstabilization of T cell microvilli contacts by chimeric antigen receptors","abstract":"T cells typically recognize their ligands using a defined cell biology-the scanning of their membrane microvilli (MV) to palpate their environment-while that same membrane scaffolds T cell receptors (TCRs) that can signal upon ligand binding. Chimeric antigen receptors (CARs) present both a therapeutic promise and a tractable means to study the interplay between receptor affinity, MV dynamics and T cell function. CARs are often built using single-chain variable fragments (scFvs) with far greater affinity than that of natural TCRs. We used high-resolution lattice lightsheet (LLS) and total internal reflection fluorescence (TIRF) imaging to visualize MV scanning in the context of variations in CAR design. This demonstrated that conventional CARs hyper-stabilized microvillar contacts relative to TCRs. Reducing receptor affinity, antigen density, and/or multiplicity of receptor binding sites normalized microvillar dynamics and synapse resolution, and effector functions improved with reduced affinity and/or antigen density, highlighting the importance of understanding the underlying cell biology when designing receptors for optimal antigen engagement.","journal":"The Journal of Cell Biology","year":2022,"id":254959,"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":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9609,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":902627,"name":"John P. Eichorst","orcid":"0000-0001-9139-9317","position":1,"is_corresponding":false},{"id":902628,"name":"Kyle Marchuk","orcid":"0000-0003-0169-7439","position":2,"is_corresponding":false},{"id":240175,"name":"En Cai","orcid":"0000-0002-8212-8387","position":3,"is_corresponding":false},{"id":727567,"name":"Carlos A. Castellanos","orcid":"0000-0003-3615-2009","position":4,"is_corresponding":false},{"id":902629,"name":"Venkataraman Sriram","orcid":"0000-0003-3433-5258","position":5,"is_corresponding":false},{"id":249364,"name":"Kole T. Roybal","orcid":"0000-0003-3030-7954","position":6,"is_corresponding":false},{"id":240181,"name":"Matthew F. Krummel","orcid":"0000-0001-7915-3533","position":7,"is_corresponding":false},{"id":240177,"name":"Casey Beppler","orcid":"0000-0001-9241-2413","position":0,"is_corresponding":true}],"reference_count":67,"raw_metadata":null,"created_at":"2026-07-19T00:25:12.987829Z","pmid":"36520493","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":[]}