To identify potential T-cell targets for Triple-Negative Breast Cancer (TNBC) vaccination, we examined the effect of the pro-inflammatory cytokine interferon-γ (IFNγ) on the transcriptome, proteome and immunopeptidome of the TNBC cell line MDA-MB-231. Using high resolution mass spectrometry, we identified in excess of 85,000 peptides from 9,647 source proteins presented by human leukocyte antigen (HLA)-I and HLA-II alleles. IFNγ resulted in increased number, diversity, and abundance of peptide antigens within the immunopeptidome, as well increasing the coverage of individual source antigens. Of note, these results were not mirrored intracellularly as we observed poor correlation of the immunopeptidomes with the cellular transcriptome and proteome. On deeper analysis of this multi-omics data, IFNγ showed remarkable induction of the antigen processing and presentation machinery including increased classical and non-classical HLA expression. In particular, HLA-E induction resulted in predicted presentation of cancer-associated and cancer specific antigens on the cell surface. Given the current lack of robust HLA-E-specific antibodies, we have pursued combined approaches to mitigate this and examine HLA-E bound peptides with greater fidelity and confidence. These findings will have significant implications on the immunotherapeutic and immunopeptidomic fields as the monomorphic nature of these molecules gives rise to potential pan cancer therapies. Furthermore, the ability of these molecules to present peptides other than leader sequences in perturbed states will fundamentally alter the way we view tumour evasion and escape.