MS-Based HLA-II Peptidomics Combined With Multiomics Will Aid the Development of Future Immunotherapies

Taylor, Hannah B.; Klaeger, Susan; Clauser, Karl R.; Sarkizova, Siranush; Weingarten-Gabbay, Shira; Graham, Daniel B.; Carr, Steven A.; Abelin, Jennifer G.

Immunotherapies have emerged to treat diseases by selectively modulating a patient’s immune response. Although the roles of T and B cells in adaptive immunity have been well studied, it remains difficult to select targets for immunotherapeutic strategies. Because human leukocyte antigen class II (HLA-II) peptides activate CD4+ T cells and regulate B cell activation, proliferation, and differentiation, these peptide antigens represent a class of potential immunotherapy targets and biomarkers. To better understand the molecular basis of how HLA-II antigen presentation is involved in disease progression and treatment, systematic HLA-II peptidomics combined with multiomic analyses of diverse cell types in healthy and diseased states is required. For this reason, MS-based innovations that facilitate investigations into the interplay between disease pathologies and the presentation of HLA-II peptides to CD4+ T cells will aid in the development of patient-focused immunotherapies.