Innate lymphoid cells and the MHC

Abstract

Innate lymphoid cells (ILCs) are a new class of immune cells that include natural killer (NK) cells and appear to be the innate counterparts to CD4(+) helper T cells and CD8(+) cytotoxic T cells based on developmental and functional similarities. Like T cells, both NK cells and other ILCs also show connections to the major histocompatibility complex (MHC). In human and mouse, NK cells recognize and respond to classical and nonclassical MHC I molecules as well as structural homologues, whereas mouse ILCs have recently been shown to express MHC II. We describe the history of MHC I recognition by NK cells and discuss emerging roles for MHC II expression by ILC subsets, making comparisons between both mouse and human when possible.

Keywords: Innate lymphoid cells; MHC; cytokines; human; human leukocyte antigen; innate; mouse.

Figure 1

Resting human and mouse NK cells are similar. MHC I recognition is encoded by genes in the KIR family of immunoglobulin-like receptors in human, and the Ly49 family of lectin-like receptors in mouse. Both human and mouse NK cells express members of the NKG2/CD94 lectin-like family, which recognize non-classical MHC I molecules. Upon activation, both human and mouse NK cells lyse targets through the release of granzymes and perforin and share production of the cytokines IFNγ, TNFα, and GM-CSF. However, activated human NK cells also can express MHC II.

Figure 2

A. NKp46⁻CCR6⁺ ILC3 engage CD44^hiCD62L^lo activated T cells in an antigen-dependent manner via MHC II. In the absence of costimulatory molecules expression by ILC3, T cells become anergic or apoptotic, which is enhanced by sequestration of IL-2 by ILC3. B. ILC2 express MHC II transcript, but also trogocytose it perhaps as well as costimulatory molecules, most likely from professional APC. In the presence of exogenous peptides or trogocytosed MHC II bound to antigen, ILC2 interact with CD4⁺ T cells and can induce their proliferation in vitro. CD4+ T cell-produced IL-2 may similarly lead to increased ILC2 proliferation and IL-13 production in vitro and in vivo.