Missing or altered self: human NK cell receptors that recognize HLA-C

Area of Science:

• Immunology
• Genetics
• Cell Biology

Background:

• Natural killer (NK) cells are crucial for innate and adaptive immunity, and placental development.
• NK cell function is controlled by interactions between killer-cell immunoglobulin-like receptors (KIRs) and their HLA ligands (HLA-A, -B, -C).
• Polymorphisms in KIR and HLA genes create diverse interactions, influencing susceptibility to various diseases.

Purpose of the Study:

• To review recent advances in understanding human-specific KIR evolution.
• To explore how KIR-HLA-C interactions regulate NK cell responses.
• To highlight the peptide selectivity of KIR for HLA-C.

Main Methods:

• Review of evolutionary, genetic, and functional studies on KIR-HLA interactions.
• Analysis of evidence for KIR peptide selectivity.
• Examination of NK cell responses to healthy, diseased, and fetal cells.

Main Results:

• KIR-HLA-C interactions are a dominant control mechanism for human NK cells.
• KIRs show selectivity for peptides presented by HLA-C, a conserved feature of activating KIRs.
• This peptide selectivity allows NK cells to detect subtle changes in the HLA-C peptidome.

Conclusions:

• KIR-HLA-C interactions are central to NK cell-mediated immunity and development.
• Peptide selectivity of KIR for HLA-C provides a nuanced regulatory mechanism for NK cells.
• Understanding KIR-HLA-C interactions is key to deciphering NK cell roles in health and disease.