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A subset of HLA-DP molecules serve as ligands for the natural cytotoxicity receptor NKp44.

ABSTRACT: Natural killer (NK) cells can recognize virus-infected and stressed cells¹ using activating and inhibitory receptors, many of which interact with HLA class I. Although early studies also suggested a functional impact of HLA class II on NK cell activity^2,3, the NK cell receptors that specifically recognize HLA class II molecules have never been identified. We investigated whether two major families of NK cell receptors, killer-cell immunoglobulin-like receptors (KIRs) and natural cytotoxicity receptors (NCRs), contained receptors that bound to HLA class II, and identified a direct interaction between the NK cell receptor NKp44 and a subset of HLA-DP molecules, including HLA-DP401, one of the most frequent class II allotypes in white populations⁴. Using NKp44ζ⁺ reporter cells and primary human NKp44⁺ NK cells, we demonstrated that interactions between NKp44 and HLA-DP401 trigger functional NK cell responses. This interaction between a subset of HLA-DP molecules and NKp44 implicates HLA class II as a component of the innate immune response, much like HLA class I. It also provides a potential mechanism for the described associations between HLA-DP subtypes and several disease outcomes, including hepatitis B virus infection^5-7, graft-versus-host disease⁸ and inflammatory bowel disease^9,10.

SUBMITTER: Niehrs A

PROVIDER: S-EPMC8370669 | biostudies-literature |

REPOSITORIES: biostudies-literature

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