Identification of post-translationally modified MHC class 1-associated peptides

ABSTRACT: Over the past three decades, the Hunt laboratory has developed advancements in mass spectrometry-based technologies to enable the identification of peptides bound to major histocompatibility complex (MHC) molecules. The MHC class I processing pathway is responsible for presenting these peptides to circulating cytotoxic T cells, allowing them to recognize and eliminate malignant cells, many of which have aberrant signaling. Professor Hunt hypothesized that due to the dysregulation in phosphorylation in cancer, that abnormal phosphopeptides are likely presented by this pathway, and went on to discover the first phosphopeptide presented by the MHC processing pathway. Thereafter, the laboratory continued to sequence MHC-associated phosphopeptides and contributed several improved methods for their enrichment, detection, and sequencing. This manuscript summarizes the most recent advancements in identification of modified MHC-associated peptides and includes the cumulative list of phosphopeptides sequenced by the Hunt lab. Further, many other post-translational modifications (PTMs) were found to modify MHC peptides, including O-GlcNAcylation, methylation, and kynurenine; in total, we present here a list of 2,450 MHC-associated PTM peptides. Many of these were disease specific and found across several patients, thus highlighting their potential as cancer immunotherapy targets. We are sharing this list with the field in hopes that it might be used in investigating this potential. Overall, the Hunt lab’s contributions have significantly advanced our understanding of antigen presentation and dysregulation of PTMs, supporting modern immunotherapy and vaccine development efforts.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Erythrocyte, B Cell, Hypopharyngeal Squamous Cell Carcinoma Cell Line, T Cell, Hepatocyte, Liver, Epithelial Cell, Skin, Colon, Bone Marrow, Embryonic Stem Cell, Blood

DISEASE(S): Colon Cancer,Squamous Cell Carcinoma,Chronic Myeloid Leukemia,Bone Marrow,Human Immunodeficiency Virus Infectious Disease,Hepatocellular Carcinoma,Skin Melanoma

SUBMITTER: Jeffrey Shabanowitz  

LAB HEAD: Jeffrey Shabanowitz

PROVIDER: PXD061414 | Pride | 2025-04-15

REPOSITORIES: Pride