The Memories of NK Cells: Innate-Adaptive Immune Intrinsic Crosstalk

Figure 2

(a) MHC class I-driven mechanisms of recognition by NK and T cells. T lymphocytes and NK cells display complementary reactions in response to MHC-I surface expression on target cells. MHC-I loaded with (foreign) peptides are necessary to bind to T cell receptor (TCR) and to activate T cells. On the contrary, the engagement of HLA-I molecules with NK MHC-I sensing inhibitory receptors (KIR and/or CD94/NKG2A) blocks NK cell responses. When NK activating receptors (NKG2D and/or NCRs) recognize their ligands on surface of target cells that lack MHC-I molecules (self-MHC-I missing recognition), NK cells kill, releasing granzymes and perforins. (b) Exploitation of NK cell missing self-recognition in the improvement of haploidentical hematopoietic stem cell transplantation. Hematopoietic stem cells (HSC) from a selected donor can generate alloreactive NK cells which are able to kill not only the patient’s neoplastic cells, but also patient dendritic cells (DCs) and T lymphocytes, reducing leukemic relapse, graft versus host disease (GvHD), and graft rejection.

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