Peptide-specific natural killer cell receptors

Abstract

Class I and II human leukocyte antigens (HLA-I and HLA-II) present peptide antigens for immunosurveillance by T cells. HLA molecules also form ligands for a plethora of innate, germline-encoded receptors. Many of these receptors engage HLA molecules in a peptide sequence independent manner, with binding sites outside the peptide binding groove. However, some receptors, typically expressed on natural killer (NK) cells, engage the HLA presented peptide directly. Remarkably, some of these receptors display exquisite specificity for peptide sequences, with the capacity to detect sequences conserved in pathogens. Here, we review evidence for peptide-specific NK cell receptors (PSNKRs) and discuss their potential roles in immunity.

Keywords: HLA-I; KIR; MHC-I; NK cell; NKG2A/C.

Figure 1.

Peptide dependent and peptide-independent MHC-I binding receptors. Peptide-dependent receptors engage the MHC-I bound peptide directly (left). Peptide independent receptors engage MHC-I outside the peptide-binding groove (right).

Figure 2.

The KIR binding site on HLA-I. (A) KIR2DL1 binds to HLA-C allotypes with the C2 epitope. KIR2DL2/3 bind HLA-C allotypes with the C1 epitope. KIR3DL1 binds to HLA-B and HLA-A allotypes with Bw4 epitope. (B) The KIR binding site is located over the C-terminal end of the HLA-I bound peptide (green). (C) The KIR binding site incorporates peptide positions 7 and 8 (p7 & p8) of 9mer peptides.