{"doi":"10.1101/2023.02.26.530125","title":"Mass spectrometric profiling of HLA-B44 peptidomes provides evidence for tapasin-mediated tryptophan editing","abstract":"T cells against pathogens and cancers involves the recognition of antigenic peptides bound to human leukocyte antigen (HLA) class-I proteins. Peptide binding to HLA class I proteins is coordinated by a multi-protein complex called the peptide loading complex (PLC). Tapasin, a key PLC component, facilitates the binding and optimization of HLA class I peptides. However, different HLA class I allotypes have variable requirements for tapasin for their assembly and surface expression. HLA-B*44:02 and HLA-B*44:05, which differ only at residue 116 of their heavy chain sequences, fall at opposite ends of the tapasin-dependency spectrum. HLA-B*44:02 (D116) is highly tapasin-dependent, whereas HLA-B*44:05 (Y116) is highly tapasinindependent. Mass spectrometric comparisons of HLA-B*4405 and HLA-B*44:02 peptidomes were undertaken to better understand the influences of tapasin upon HLA-B44 peptidome compositions. Analyses of the HLA-B*44:05 peptidomes in the presence and absence of tapasin reveal that peptides with the C-terminal tryptophan residues and those with higher predicted binding affinities are selected in the presence of tapasin. Additionally, when tapasin is present, C-terminal tryptophans are also more highly represented among peptides unique to B*44:02 and those shared between B*44:02 and B*44:05, compared with peptides unique to B*44:05. Overall, our findings demonstrate that tapasin influences the C-terminal composition of HLA class I-bound peptides and favors the binding of higher affinity peptides. For the HLA-B44 family, the presence of tapasin or high tapasin-dependence of an allotype results in better binding of peptides with C-terminal tryptophans, consistent with a role for tapasin in stabilizing an open conformation to accommodate bulky C-terminal residues.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":403327,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9575,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1134797,"name":"Avrokin Surnilla","orcid":null,"position":1,"is_corresponding":false},{"id":506788,"name":"Anita Zaitouna","orcid":"0000-0001-5513-6886","position":2,"is_corresponding":false},{"id":253569,"name":"Venkatesha Basrur","orcid":"0000-0002-0853-9655","position":3,"is_corresponding":false},{"id":667834,"name":"Michael B. Mumphrey","orcid":"0000-0003-3150-8694","position":4,"is_corresponding":false},{"id":301029,"name":"Irina Grigorova","orcid":"0000-0002-4963-7403","position":5,"is_corresponding":false},{"id":108226,"name":"Marcin Cieślik","orcid":"0000-0002-5467-1040","position":6,"is_corresponding":false},{"id":37727,"name":"Mary Carrington","orcid":"0000-0002-2692-2180","position":7,"is_corresponding":false},{"id":51780,"name":"Alexey I. Nesvizhskii","orcid":"0000-0002-2806-7819","position":8,"is_corresponding":false},{"id":292652,"name":"Malini Raghavan","orcid":"0000-0002-1345-9318","position":9,"is_corresponding":false},{"id":506789,"name":"Amanpreet Kaur","orcid":"0000-0001-6806-8448","position":0,"is_corresponding":true}],"reference_count":39,"raw_metadata":null,"created_at":"2026-07-19T01:20:36.280647Z","pmid":"36909546","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":[]}