The HLA-Ligand-Atlas. A resource of natural HLA ligands presented on benign tissues

The human leukocyte antigen (HLA) complex regulates the adaptive immune response by showcasing the intracellular and extracellular protein content to the immune system. T cells recognize these HLA-presented peptides as self or foreign and can elicit an immune response. In this work, we describe the HLA-Ligand-Atlas, a comprehensive map of HLA-I and HLA-II-presented peptides from 30 benign tissues, 51 HLA-I alleles, and 86 HLA-II alleles. Nearly 50% of HLA ligands have not been previously described. Due to the scarcity of benign human samples, the tissue was extracted from different organs at autopsy from human subjects without any diagnosed malignancy. Furthermore, we were able to identify non-canonical HLA-I peptides on benign tissues, showing that their processing is not unique to cancer. This dataset holds great promise in answering both basic and translational questions in fields such as autoimmunity, organ/tissue transplantation, and cancer immunotherapy.