Researchers identify unique cell receptors, potential for new therapies

Researchers from the University of Colorado Anschutz Medical Campus have identified a potential new immune checkpoint receptor that could lead to treatments for diseases such as lung and bowel cancer and autoimmune conditions including IBD.

The study examines a family of 13 receptors or proteins that transmit signals for cells to follow, called killer cell immunoglobulin-like receptors (KIR). Of the 13 receptors, one is unique in that it has not readily been observed in the immune cells of peripheral blood. Researchers identified that this mysterious receptor, called KIR3DL3, is found in the intestine and lungs, suggesting it could provide signals specifically required by immune cells that are resident in mucosal tissues.

Researchers were able to determine the tissue distribution of the elusive KIR3DL3 receptor by searching for a sequence of nucleotides specific to KIR3DL3 in public RNA sequencing databases. After developing a short list of probable tissues where KIR3DL3 could be expressed, they collaborated with lab groups in the United Kingdom that created a KIR3DL3-specific antibody, and colleagues from the University of Colorado School of Medicine who supplied the tissues. Using this antibody, the researchers confirmed KIR3DL3 protein expression was rare in peripheral blood and most common in the intestine.

To assess the functional attributes of KIR3DL3-expressing cells, the researchers used flow cytometry and single-cell RNA sequencing. These approaches identified KIR3DL3 expression in a unique population of T cells with hallmarks suggestive of recent activation. In a series of functional experiments, they found that when KIR3DL3 is activated by its binding partner, HHLA2, it transmits a signal that can inhibit immune responses.

Reference: Billy Palmer et al, Science Immunology, UNIVERSITY OF COLORADO ANSCHUTZ MEDICAL CAMPUS