IGSF8 is an innate immune checkpoint and cancer immunotherapy target.

Antigen presentation defects in tumors are prevalent mechanisms of adaptive immune evasion and resistance to cancer immunotherapy, whereas how tumors evade innate immunity is less clear. Using CRISPR screens, we discovered that IGSF8 expressed on tumors suppresses NK cell function by interacting with human KIR3DL2 and mouse Klra9 receptors on NK cells. IGSF8 is normally expressed in neuronal tissues and is not required for cell survival in vitro or in vivo.

Mapping antibody binding using multiplexed epitope substitution analysis.

A more complete understanding of antibody epitopes would aid the development of diagnostics, therapeutic antibodies, and vaccines. However, current methods for mapping antibody binding to epitopes require a targeted experimental approach, which limits throughput. To address these limitations, we developed Multiplexed Epitope Substitution Analysis (MESA) which can rapidly characterize various distinct epitopes using millions of antibody-binding peptides.

A general approach for predicting protein epitopes targeted by antibody repertoires using whole proteomes.

Antibodies are essential to functional immunity, yet the epitopes targeted by antibody repertoires remain largely uncharacterized. To aid in characterization, we developed a generalizable strategy to predict antibody-binding epitopes within individual proteins and entire proteomes. Specifically, we selected antibody-binding peptides for 273 distinct sera out of a random library and identified the peptides using next-generation sequencing.