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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\u2013bound 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.<\/jats:p>","DOI":"10.4049\/jimmunol.2300232","type":"journal-article","created":{"date-parts":[[2023,9,22]],"date-time":"2023-09-22T09:16:43Z","timestamp":1695374203000},"page":"1298-1307","source":"Crossref","is-referenced-by-count":5,"title":["Mass Spectrometric Profiling of HLA-B44 Peptidomes Provides Evidence for Tapasin-Mediated Tryptophan Editing"],"prefix":"10.1093","volume":"211","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6806-8448","authenticated-orcid":false,"given":"Amanpreet","family":"Kaur","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Michigan Medical School , Ann Arbor, MI"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Avrokin","family":"Surnilla","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Michigan Medical School , Ann Arbor, MI"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anita J","family":"Zaitouna","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Michigan Medical School , Ann Arbor, MI"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael B","family":"Mumphrey","sequence":"additional","affiliation":[{"name":"Department of Computational Medicine and Bioinformatics, University of Michigan Medical School , Ann Arbor, MI"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0853-9655","authenticated-orcid":false,"given":"Venkatesha","family":"Basrur","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Michigan Medical School , Ann Arbor, MI"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4963-7403","authenticated-orcid":false,"given":"Irina","family":"Grigorova","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Michigan Medical School , Ann Arbor, MI"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcin","family":"Cieslik","sequence":"additional","affiliation":[{"name":"Department of Computational Medicine and Bioinformatics, University of Michigan Medical School , Ann Arbor, MI"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2692-2180","authenticated-orcid":false,"given":"Mary","family":"Carrington","sequence":"additional","affiliation":[{"name":"Basic Science Program, Frederick National Laboratory for Cancer Research, National Cancer Institute , Frederick, MD"},{"name":"Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute , Bethesda, MD"},{"name":"Ragon Institute of MGH, MIT and Harvard , Cambridge, MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2806-7819","authenticated-orcid":false,"given":"Alexey I","family":"Nesvizhskii","sequence":"additional","affiliation":[{"name":"Department of Computational Medicine and Bioinformatics, University of Michigan Medical School , Ann Arbor, MI"},{"name":"Department of Pathology, University of Michigan Medical School , Ann Arbor, MI"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1345-9318","authenticated-orcid":false,"given":"Malini","family":"Raghavan","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Michigan Medical School , Ann Arbor, MI"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,9,22]]},"reference":[{"key":"2025020406162330100_r1","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/978-981-13-9367-9_2","article-title":"MHC molecules, T cell receptors, natural killer cell receptors, and viral immunoevasins\u2014key elements of adaptive and innate immunity","volume":"1172","author":"Jiang","year":"2019","journal-title":"Adv. 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