Peptides bound to major histocompatibility complexes (MHC) play a critical role in immune cell recognition and can trigger an antitumor immune response in cancer. Surface MHC levels can be modulated by anticancer agents, altering immunity. However, understanding the peptide repertoire’s response to treatment remains challenging and is limited by quantitative mass spectrometry-based strategies lacking normalization controls. The White lab has developed a novel platform for profiling the peptide MHC (pMHC) repertoire, leveraging recombinant heavy isotope-coded peptide standards (hipMHCs) and multiplex isotope tagging for highly accurate relative and absolute quantification of pMHC levels across samples. We utilize this platform, as well as traditional immunopeptidomics workflows, to characterize pMHC repertoires across different disease states, cell types, and therapeutic perturbations, with the goal of identifying targetable antigens that are differentially regulated in response to therapy. We also use immunopeptidomics in concert with other MS-based methods to untangle the rules guiding antigen presentation. Additional ongoing studies in the lab aim to further characterize pMHC repertoire changes, which may enable predictions as to how to tune the immunopeptidome to be most applicable to immunotherapy targeting.

Recent publications:

Stopfer LE, Mesfin JM, Joughin BA, Lauffenburger DA, White FM. Multiplexed relative and absolute quantitative immunopeptidomics reveals MHC I repertoire alterations induced by CDK4/6 inhibition. Nat Commun. 2020;11(1):2760.

Jaeger AM, Stopfer L, Lee S, Gaglia G, Sandel D, Santagata S, Lin NU, Trepel JB, White F, Jacks T, Lindquist S, Whitesell L. Rebalancing protein homeostasis enhances tumor antigen presentation. Clin Cancer Res. 2019;25(21):6392-6405.