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Updated: Aug 18, 2026

Use of Single Chain MHC Technology to Investigate Co-agonism in Human CD8+ T Cell Activation
Published on: February 28, 2019
Human cytolytic T lymphocytes expressing HLA class-I-specific inhibitory receptors
Maria Cristina Mingari1, Gabriella Pietra, Lorenzo Moretta
1Istituto Nazionale per la Ricerca sul Cancro, L.go Rosanna Benzi, 10, 16132 Genova, Italy. mariacristina.mingari@istge.it
MHC class-1-specific inhibitory receptors were originally described in NK cells, in which they represent an important fail-safe mechanism that induces NK cell tolerance to normal self cells. These inhibitory NK receptors (iNKRs) were subsequently found expressed on different T cell subsets, primarily CD8(+) cytolytic T lymphocytes (CTLs), in which they can inhibit T cell receptor mediated functions. Some iNKR(+) CTLs are HLA-E-restricted, represent oligo- or monoclonal expansions, and can play a defensive role in viral infections. Although T cell activation, in the presence of certain cytokines, can induce the expression of the CD94-NKG2A heterodimeric receptor, the mechanism leading to the expression of killer immunoglobulin-like receptors (KIRs) is still unknown. The expression of iNKRs in T cells might contribute to the prevention of apoptotic cell death, thus allowing their survival and clonal expansion in vivo. In addition, iNKR(+) T cells might contribute to peripheral self-tolerance.
MHC class-1-specific inhibitory receptors were originally described in NK cells, in which they represent an important fail-safe mechanism that induces NK cell tolerance to normal self cells. These inhibitory NK receptors (iNKRs) were subsequently found expressed on different T cell subsets, primarily CD8(+) cytolytic T lymphocytes (CTLs), in which they can inhibit T cell receptor mediated functions. Some iNKR(+) CTLs are HLA-E-restricted, represent oligo- or monoclonal expansions, and can play a defensive role in viral infections. Although T cell activation, in the presence of certain cytokines, can induce the expression of the CD94-NKG2A heterodimeric receptor, the mechanism leading to the expression of killer immunoglobulin-like receptors (KIRs) is still unknown. The expression of iNKRs in T cells might contribute to the prevention of apoptotic cell death, thus allowing their survival and clonal expansion in vivo. In addition, iNKR(+) T cells might contribute to peripheral self-tolerance.
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