The CD94/NKG2C killer lectin-like receptor constitutes an alternative activation pathway for a subset of CD8+ T cells

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Abstract
The CD94/NKG2C killer lectin‐like receptor (KLR) specific for HLA‐E is coupled to the KARAP/DAP12 adapter in a subset of NK cells, triggering their effector functions. We have studied the distribution and function of this KLR in T lymphocytes. Like other NK cell receptors (NKR), CD94/NKG2C was predominantly expressed by a CD8+ T cell subset, though TCRγδ+ NKG2C+ and rare CD4+ NKG2C+ cells were also detected in some individuals. Coculture with the 721.221 HLA class I‐deficient lymphoma cell line transfected with HLA‐E (.221‐AEH) induced IL‐2Rα expression in CD94/NKG2C+ NK cells and a minor subset of CD94/NKG2C+ T cells, promoting their proliferation; moreover, a similar response was triggered upon selective engagement of CD94/NKG2C with a specific mAb. CD8+ TCRαβ CD94/NKG2C+ T cell clones, that displayed different combinations of KIR and CD85j receptors, expressed KARAP/DAP12 which was co‐precipitated by an anti‐CD94 mAb. Specific engagement of the KLR triggered cytotoxicity and cytokine production in CD94/NKG2C+ T cell clones, inducing as well IL‐2Rα expression and a proliferative response. Altogether these results support that CD94/NKG2C may constitute an alternative T cell activation pathway capable of driving the expansion and triggering the effector functions of a CTL subset.