Table 1.
KIR and HLA genotypes related to HIV-1 outcome
| HIV-1 outcome | Receptor/ligand | Mechanism | Ref | |
|---|---|---|---|---|
| HIV-1 resistance | KIR3DS1/S1 | HLA-Bw4 | No/less inhibition and increased activation, promoting faster NK cell activation | [85, 86] |
| KIR3DS1/x | HLA-Bw4 | No/less inhibition and increased activation, promoting faster NK cell activation | [87] | |
| KIR3DS1/L1 | Higher activating ratio, stronger NK cell response | [84] | ||
| KIR3DL1*h | HLA-B*57 | “Amplified” education, resulting in stronger NK cell response in absence of ligand | [72] | |
| KIR3DL1 | Bw4 | Educated KIR3DL1+ NK cells had increased anti-HIV-1 ADCC mediated cytotoxicity against allogeneic target cells | [76] | |
| KIR3DL1 | HLA-Bw6/Bw6 | Absence/lowering of inhibitory threshold, promoting faster NK cell activation | [88] | |
| KIR2DL2/3 | HLA-C2/C2 | Absence/lowering of inhibitory threshold | [88] | |
| KIR2DS4del | Unknown | Unpublished | ||
| KIR2DL1 | HLA-C2 | Absence of HLA-C2 expression by allogeneic target cells induces cytotoxicity based on KIR/HLA mismatch | [6] | |
| Haplotype B/x | Multiple aKIRs inducing stronger response | [6, 84–88] | ||
| Slower disease progression | KIR3DS1 | HLA-Bw4-80I | Slower disease progression; Robust expansion during early infection; Inhibition in vitro viral replication | [59–61] |
| Increase of copy numbers is associated with inhibition of viral replication | [62] | |||
| In vitro production of viral inhibiting chemokines (CCL3-5), preventing HIV-1 entry | [123] | |||
| KIR3DS1 | HLA-B*57/58 | Lower CD38-expression, increased degranulation and IFN-γ production | [64] | |
| KIR3DS1 | Associated with higher CD4+ T-cell counts | [63] | ||
| KIR3DL1/S1 | HLA-Bw4 | KIR3DL1-dose dependent-licensed NK cells exert cytotoxicity via KIR3DS1-mediated activation | [66] | |
| KIR3DL1 | HLA-Bw4 | Increased polyfunctionality by KIR3DL1 licensed NK cells | [65] | |
| Educated KIR3DL1+ NK cells had increased anti-HIV-1 ADCC mediated activation | [75] | |||
| KIR3DL1*h | HLA-Bw4-80I | Delayed progression to AIDS, increased degranulation, TNF and IFN-γ production | [66, 67] | |
| KIR3DL1*h | HLA-B*57 | “Amplified” education, resulting in strong NK cell response, increased NK cell trifunctionality | [66, 68, 69] | |
| In vitro production of viral inhibiting chemokines (CCL3-5), preventing HIV-1 entry | [123] | |||
| KIR3DL1*004 | HLA-Bw4 | Absence/lowering of inhibitory threshold, because of intracellular expression of KIR3DL1 | [66] | |
| KIR2DL3 | HLA-C1 | Lower viral load and higher CD4 count associated with HIV-1 specific NK cell responses | [73] | |
| KIR2DL4 | CD4+ T-cell preservation, higher copy number resulting in increased IFN-γ production in SIV-infection | [124] | ||
| Rapid disease progression | KIR3DS1 | HLA-Bw4-80I | Rapid progression, no education of KIR3DS1 expressing NK cells | [80] |
| KIR3DS1(/S1) | Rapid progression, robust immune activation accelerating disease progression | [59, 80] | ||
| KIR2DS2/3 | Rapid progression, robust immune activation accelerating disease progression | [80] | ||
| KIR2DS4*001 | High viral load and accelerated HIV-1 transmission, immune activation accelerating disease progression | [82] | ||
| KIR2DL2/3 | HLA-C1 | Higher viral load and increased mortality | [83] | |
| Haplotype B/x | Rapid progression, robust immune activation accelerating disease progression | [80, 81] | ||
Summarization of the KIR, HLA or KIR-HLA haplo-/genotypes associated with HIV-1 resistance and disease progression towards AIDS. HLA class I genotypes associated with altered HIV-1 outcome are not included as its function is not solely relevant for NK cell responses but also for CD8+ T cell responses. Additional data in Table 1 obtained from [123] and [124]