We have addressed these limitations with ARTEMIS: a simple, robust, and flexible platform for peptide discovery across ligandomes, optionally including specific proteins-of-interest, that combines novel, secreted HLA-I discovery reagents spanning multiple alleles, optimized lentiviral transduction, and streamlined affinity-tag purification to improve upon conventional methods.
This platform fills a middle ground between existing techniques: sensitive and adaptable, but easy and affordable enough to be widely employed by general laboratories. The mammalian immune system surveils cellular proteomes through recognition of peptide fragments of endogenous proteins bound to extracellular HLA class one proteins HLA-I , thus detecting intracellular infection or transformation events 1.
Therefore, a cellular ligandome only represents a tiny percentage of all possible proteome-derived peptides. Peptides from self-proteins populate the ligandome in the absence of disease but peptides from pathogen or tumor proteins are added during infection or cancer.
T cell responses to self-peptide pHLAs can also be involved in the initiation and progression of autoimmune diseases 6. The ligandome is highly unevenly distributed across constituent peptides, temporally dynamic, and affected by cell type, the cellular environment, disease state, and the peptide specificity of the HLA alleles comprising the cellular haplotype.
From a translational perspective, the ability to identify and define disease-specific HLA-I restricted peptides enables diagnosis and treatment. Many potent cancer immunotherapies target HLA-I presented peptides derived from oncogenic viruses, tumor-specific mutations neoantigens , or aberrantly expressed tumor-associated proteins, yielding exquisitely focused treatments 8.
