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While \u03b22m's structural role is well established, its influence on the antigenic landscape remains incompletely understood. Here, we investigated how constitutive \u03b22m binding to HLA\u2010I influences the antigenic landscape in the context of cancer\u2010associated epitopes. Using two engineered cell lines expressing \u03b22m fused to the HLA\u2010I heavy chain, we analysed changes in immunopeptidomes and epitope presentation. Despite cell line\u2013specific transcriptional responses, the fusion of \u03b22m to HLA\u2010I consistently reduced peptide editing and resulted in convergent remodelling of the antigen presentation pathway (APP). The fusion further altered peptide selection, favouring the display of lower\u2010affinity peptides derived from endogenous proteins while impairing high\u2010affinity peptide presentation on HLA\u2010I molecules. These changes were not attributable to APP component abundance but rather reflected mechanistic alterations in peptide selection and impacted T cell receptor recognition of tumour epitopes. Our findings suggest that \u03b22m\u2013HLA\u2010I fusion can distort the physiological antigenic repertoire and T cell recognition, with implications for epitope discovery, immunotherapy design, and studies of HLA\u2010I\u2013mediated immune surveillance.<\/jats:p>","DOI":"10.1002\/eji.70210","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T06:47:17Z","timestamp":1779950837000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Stable \u03b22\u2010Microglobulin\u2013HLA Class I Association Reshapes the Antigenic Landscape and TCR Recognition of Cancer\u2010Associated Epitopes"],"prefix":"10.1002","volume":"56","author":[{"given":"Ana","family":"Barajas Molina","sequence":"first","affiliation":[{"name":"Molecular Immunology laboratory The Francis Crick Institute  London UK"},{"name":"Centre for Inflammation Biology and Cancer Immunology &amp; Peter Gorer Department of 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