Immunopeptidomes are the peptide repertoires bound by the molecules encoded by the major histocompatibility complex (MHC) (human leukocyte antigen (HLA) in humans). These HLA-peptide complexes are presented on the cell surface for immune T cell recognition. Immunopeptidomics utilizes tandem mass spectrometry (MS/MS) to identify and quantify peptides bound to HLA molecules. The dataset deposited here contains the DDA runs used to generate the spectral libraries of the HLA-bound peptides purified and isolated from C1R-B*57:01 and C1R-A*02:01 cell lines.