{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kaur A"],"funding":["HHS | National Institutes of Health","NIAID NIH HHS","HHS | NIH | National Cancer Institute","NHGRI NIH HHS","HHS | NIH | National Institute of Allergy and Infectious Diseases","NCI NIH HHS","NIGMS NIH HHS"],"pagination":["1298-1307"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10592002"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["211(9)"],"pubmed_abstract":["The extreme polymorphisms of HLA class I proteins result in structural variations in their peptide binding sites to achieve diversity in Ag presentation. External factors could independently constrict or alter HLA class I peptide repertoires. Such effects of the assembly factor tapasin were assessed for HLA-B*44:05 (Y116) and a close variant, HLA-B*44:02 (D116), which have low and high tapasin dependence, respectively, for their cell surface expression. Analyses of the HLA-B*44:05 peptidomes in the presence and absence of tapasin reveal that peptides with C-terminal tryptophans and higher predicted affinities are preferentially selected by tapasin, coincident with reduced frequencies of peptides with other C-terminal amino acids, including leucine. Comparisons of the HLA-B*44:05 and HLA-B*44:02 peptidomes indicate the expected structure-based alterations near the peptide C termini, but also C-terminal amino acid frequency and predicted affinity changes among the unique and shared peptide groups for B*44:02 and B*44:05. Overall, these findings indicate that the presence of tapasin and the tapasin dependence of assembly alter HLA class I peptide-binding preferences at the peptide C terminus. The particular C-terminal amino acid preferences that are altered by tapasin are expected to be determined by the intrinsic peptide-binding specificities of HLA class I allotypes. Additionally, the findings suggest that tapasin deficiency and reduced tapasin dependence expand the permissive affinities of HLA class I-bound peptides, consistent with prior findings that HLA class I allotypes with low tapasin dependence have increased breadth of CD8+ T cell epitope presentation and are more protective in HIV infections."],"journal":["Journal of immunology (Baltimore, Md. : 1950)"],"pubmed_title":["Mass Spectrometric Profiling of HLA-B44 Peptidomes Provides Evidence for Tapasin-Mediated Tryptophan Editing."],"pmcid":["PMC10592002"],"funding_grant_id":["T32 AI007528","R01 GM094231","R21 AI126054","75N91019D00024","R21AI164025","R21 AI164025","R01 AI044115","T32 AI007413","R01AI044115","R01GM94231","T32AI007413","T32 HG000040","T32 CA140044","U24 CA271037","T32AI007528","U24CA271037"],"pubmed_authors":["Mumphrey MB","Basrur V","Zaitouna AJ","Raghavan M","Carrington M","Surnilla A","Grigorova I","Kaur A","Cieslik M","Nesvizhskii AI"],"additional_accession":[]},"is_claimable":false,"name":"Mass Spectrometric Profiling of HLA-B44 Peptidomes Provides Evidence for Tapasin-Mediated Tryptophan Editing.","description":"The extreme polymorphisms of HLA class I proteins result in structural variations in their peptide binding sites to achieve diversity in Ag presentation. External factors could independently constrict or alter HLA class I peptide repertoires. Such effects of the assembly factor tapasin were assessed for HLA-B*44:05 (Y116) and a close variant, HLA-B*44:02 (D116), which have low and high tapasin dependence, respectively, for their cell surface expression. Analyses of the HLA-B*44:05 peptidomes in the presence and absence of tapasin reveal that peptides with C-terminal tryptophans and higher predicted affinities are preferentially selected by tapasin, coincident with reduced frequencies of peptides with other C-terminal amino acids, including leucine. Comparisons of the HLA-B*44:05 and HLA-B*44:02 peptidomes indicate the expected structure-based alterations near the peptide C termini, but also C-terminal amino acid frequency and predicted affinity changes among the unique and shared peptide groups for B*44:02 and B*44:05. Overall, these findings indicate that the presence of tapasin and the tapasin dependence of assembly alter HLA class I peptide-binding preferences at the peptide C terminus. The particular C-terminal amino acid preferences that are altered by tapasin are expected to be determined by the intrinsic peptide-binding specificities of HLA class I allotypes. Additionally, the findings suggest that tapasin deficiency and reduced tapasin dependence expand the permissive affinities of HLA class I-bound peptides, consistent with prior findings that HLA class I allotypes with low tapasin dependence have increased breadth of CD8+ T cell epitope presentation and are more protective in HIV infections.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Nov","modification":"2026-06-02T22:13:13.026Z","creation":"2025-04-06T14:25:45.81Z"},"accession":"S-EPMC10592002","cross_references":{"pubmed":["37737643"],"doi":["10.4049/jimmunol.2300232"]}}