{"doi":"10.1172/jci144864","title":"Beryllium-specific CD4+ T cells induced by chemokine neoantigens perpetuate inflammation","abstract":"Discovering dominant epitopes for T cells, particularly CD4+ T cells, in human immune-mediated diseases remains a significant challenge. Here, we used bronchoalveolar lavage (BAL) cells from HLA-DP2-expressing patients with chronic beryllium disease (CBD), a debilitating granulomatous lung disorder characterized by accumulations of beryllium-specific (Be-specific) CD4+ T cells in the lung. We discovered lung-resident CD4+ T cells that expressed a disease-specific public CDR3β T cell receptor motif and were specific to Be-modified self-peptides derived from C-C motif ligand 4 (CCL4) and CCL3. HLA-DP2-CCL/Be tetramer staining confirmed that these chemokine-derived peptides represented major antigenic targets in CBD. Furthermore, Be induced CCL3 and CCL4 secretion in the lungs of mice and humans. In a murine model of CBD, the addition of LPS to Be oxide exposure enhanced CCL4 and CCL3 secretion in the lung and significantly increased the number and percentage of CD4+ T cells specific for the HLA-DP2-CCL/Be epitope. Thus, we demonstrate a direct link between Be-induced innate production of chemokines and the development of a robust adaptive immune response to those same chemokines presented as Be-modified self-peptides, creating a cycle of innate and adaptive immune activation.","journal":"Journal of Clinical Investigation","year":2021,"id":179212,"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":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9652,"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":225728,"name":"Jeremy Chase Crawford","orcid":"0000-0003-4096-6048","position":1,"is_corresponding":false},{"id":661584,"name":"Alex N. Tinega","orcid":"0000-0001-7234-3115","position":2,"is_corresponding":false},{"id":463865,"name":"Laurie G. Landry","orcid":"0000-0002-4064-9109","position":3,"is_corresponding":false},{"id":345658,"name":"Frances Crawford","orcid":"0000-0003-3282-0508","position":4,"is_corresponding":false},{"id":661583,"name":"Douglas G. Mack","orcid":"0000-0001-8318-747X","position":5,"is_corresponding":false},{"id":726635,"name":"Arlan D. Martin","orcid":null,"position":6,"is_corresponding":false},{"id":303831,"name":"Shaikh M. Atif","orcid":"0000-0002-7928-5365","position":7,"is_corresponding":false},{"id":607964,"name":"Li Li","orcid":"0000-0002-4712-2692","position":8,"is_corresponding":false},{"id":661579,"name":"Radleigh G. Santos","orcid":"0000-0002-8194-5502","position":9,"is_corresponding":false},{"id":369808,"name":"Maki Nakayama","orcid":"0000-0002-0009-3687","position":10,"is_corresponding":false},{"id":345662,"name":"John W. Kappler","orcid":"0000-0002-5827-6240","position":11,"is_corresponding":false},{"id":530647,"name":"Lisa A. Maier","orcid":"0000-0001-6872-1769","position":12,"is_corresponding":false},{"id":225737,"name":"Paul G. Thomas","orcid":"0000-0001-7955-0256","position":13,"is_corresponding":false},{"id":106918,"name":"Clemencia Pinilla","orcid":"0000-0002-6174-8114","position":14,"is_corresponding":false},{"id":459147,"name":"Andrew P. Fontenot","orcid":"0000-0003-4095-512X","position":15,"is_corresponding":false},{"id":661581,"name":"Michael T. Falta","orcid":"0000-0002-0835-6904","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":null,"created_at":"2026-07-18T23:47:44.875897Z","pmid":"33630763","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":[]}