The Efficiency of the Human CD8+ T Cell Response: How Should We Quantify It, What Determines It, and Does It Matter?
Figure 2
Proposed mechanism to explain inhibitory KIR enhancement of HLA class I associations.
KIR-HLA associations are typically attributed to direct NK action (a). However, Seich al Basatena's observations do not appear to be compatible with direct NK killing for four reasons. Firstly, most of the HLA molecules which were enhanced do not bind KIR2DL2. Secondly, both protective and detrimental HLA associations were enhanced. Thirdly, KIR2DL2 with or without its C1 ligand (i.e., not in the context of a particular protective or detrimental HLA allele) had no effect on any outcome for HCV or HTLV-1. And finally, the protective effect of binding HBZ was enhanced, and NK cells display some peptide specificity, but such marked protein specificity is more reminiscent of T cells [56]. Instead they hypothesise that the downstream effectors are CD8+ T cells (b). They postulate that KIR2DL2 enhances CD8+ T cell responses by increasing the survival of memory CD8+ T cells. Either because (i) inhibitory KIR on CD8+ T cells are associated with reduced activation induced cell death and protection from exhaustion [77]–[79] or (ii) inhibitory KIR on NK cells reduce NK-killing of activated CD8+ T cells [80], [81].