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  • Title: Exploitation of alloreactive NK cells in adoptive immunotherapy of cancer.
    Author: Ruggeri L, Mancusi A, Capanni M, Martelli MF, Velardi A.
    Journal: Curr Opin Immunol; 2005 Apr; 17(2):211-7. PubMed ID: 15766683.
    Abstract:
    NK cells are primed to kill by several activating receptors. Killing of autologous cells is prevented as NK cells co-express inhibitory receptors for self-MHC class I molecules. Human NK cells discriminate between different allelic forms of MHC molecules via killer cell immunoglobulin-like receptors (KIRs), which are clonally distributed, and each cell in the repertoire bears at least one receptor that is specific for self-MHC class I molecules. Consequently, when faced with mismatched allogeneic targets, NK cells in the repertoire will sense the missing expression of self-MHC class I alleles and will mediate alloreactions. Recent studies in murine transplant models and data from mismatched haematopoietic transplant trials demonstrate MHC class I mismatches, which generate an alloreactive NK-cell response in the graft-versus-host direction, eradicate leukaemia, improve engraftment and protect against T-cell-mediated graft-versus-host disease.
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