Mass spectrometric profiling of HLA-B44 peptidomes provides evidence for Tapasin-mediated Tryptophan editing

نویسندگان

چکیده

Abstract Activation of CD8 +T cells against pathogens and cancers involves the recognition antigenic peptides presented in complex with human leukocyte antigen (HLA) class-I proteins. Peptide binding to HLA-I proteins is coordinated by a multi-protein called peptide loading (PLC). Tapasin, key PLC component, facilitates optimization peptides. However, different allotypes have variable requirements for tapasin their assembly surface expression. HLA-B*44:02 HLA-B*44:05, which differ only at position 116 heavy chain sequences, fall opposite ends tapasin-dependency spectrum. (D116) highly tapasin-dependent, whereas HLA-B*44:05 (Y116) tapasin-independent. To better understand influences upon HLA-B44 peptidome compositions, we undertook mass spectrometric comparisons HLA-B*44:02/05 peptidomes under tapasin-sufficient and/or tapasin-deficient conditions. Analyses presence vs. absence reveal that increases frequency C-terminal tryptophan residues. In tapasin, tryptophans are also more represented among unique B*44:02 those shared between B*44:05, compared B*44:05. Overall, our findings demonstrate composition HLA-I-bound For family, or high tapasin-dependence an allotype results tryptophans, consistent role stabilizing open conformation accommodate bulky Supported grants from NIH Malini Raghavan (R21 AI164025, R21 AI126054 R01AI044115)

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ژورنال

عنوان ژورنال: Journal of Immunology

سال: 2023

ISSN: ['1550-6606', '0022-1767']

DOI: https://doi.org/10.4049/jimmunol.210.supp.221.14