Table 2.
Associations of NK education in human health and disease
| KIR-HLA combination |
Education status |
Health/Disease state |
Impact |
|---|---|---|---|
| KIR2DL1 + HLA-C2 | Educated | Pregnancy | Increased risk of pre-eclampsia, stillbirth and low birthweight (especially with fetal HLA-C2) [50,93,94] |
|
|
|||
| Infectious disease | Enriched among individuals acquiring Dengue virus infection [95] | ||
|
|
|||
| Infectious disease | Enriched among HCMV seropositive NKG2C+ cells in persons with HCMV [74] | ||
|
|
|||
| KIR2DL1 without HLA-C2 | Uneducated | Infectious disease | Lower reactivation of HCMV after kidney transplant [96] |
|
|
|||
| Cancer | Protective against AML relapse following allogeneic HCT in patients with AML (missing ligand) [83,97] | ||
|
| |||
| KIR2DL2 + HLA-C1 | Strongly educated | Autoimmune disease | Protection against ulcerative colitis [98] |
|
|
|||
| Inflammatory disease | Enriched in patients with Kawasaki disease [99] | ||
|
|
|||
| Cancer/infectious disease | Associated with younger age of onset for hepatocellular carcinoma in persons infected with hepatitis B [100] | ||
|
|
|||
| Infectious disease/cancer | Enriched among persons infected with high-risk human papillomavirus and patients developing invasive cervical cancer [101] | ||
|
|
|||
| Cancer | Protection against relapse of hematological malignancy in patients receiving umbilical cord blood transplantation [102] | ||
|
| |||
| KIR2DL2 + HLA-C2 | Uneducated – weakly educated | Infectious disease | Lower reactivation of HCMV after kidney transplant [96] |
|
|
|||
| Autoimmune disease | Increased susceptibility to type I diabetes [103] | ||
|
| |||
| KIR2DS1 + HLA-C2 | Educated (tolerogenic) | Pregnancy | Enriched in patients with recurrent miscarriage [49] |
|
|
|||
| Autoimmune disease | Protective against multiple sclerosis [67] | ||
|
| |||
| KIR2DS1, without HLA-C2 | Uneducated (reactive) | Pregnancy | Enriched in patients with failed pregnancy after in vitro fertilization [105] |
|
|
|||
| Cancer | Protection against AML relapse after hematopoietic cell transplantation [104] | ||
|
|
|||
| Cancer | Protection against relapse of hematological malignancy in patients receiving umbilical cord blood transplantation [102] | ||
|
| |||
| KIR2DL3 + HLA-C1 | Educated | Infectious disease | increased resolution of HCV infection compared with 2DL2+C1 or 2DL1+C2; possibly due to weaker inhibitory signals [106] |
|
|
|||
| Infectious disease | Resistance to Ebola infection [107] | ||
|
|
|||
| Infectious disease | Higher incidence of cerebral malaria in infected persons [108] | ||
|
|
|||
| Infectious disease | Underrepresented among individuals acquiring Dengue virus infection [95] | ||
|
|
|||
| Infectious disease | Enriched among patients resolving hepatitis B infection; underrepresented in patients with chronic hepatitis B infection [109] | ||
|
|
|||
| Infectious disease | Enriched among HCMV seropositive NKG2C+ cells in persons with HCMV [74] | ||
|
|
|||
| Infectious disease/cancer | Enriched among persons infected with high-risk human papillomavirus and patients developing invasive cervical cancer [101] | ||
|
|
|||
| Cancer | Protection against relapse of hematological malignancy in patients receiving umbilical cord blood transplantation [102] | ||
|
| |||
| KIR2DS2 + HLA-C1 | Infectious disease | Protective against HCV and Dengue virus [110] | |
|
| |||
| KIR2DL3 without HLA-C1 | Uneducated | Autoimmune disease | Protection against ulcerative colitis [98] |
|
|
|||
| Cancer | Protection against AML relapse in patients receiving hematopoietic cell transplantation [102,104,111] | ||
|
| |||
| KIR3DL1 + HLA-Bw4 | Educated | Infectious disease | High affinity pairs (KIR3DL1-high + HLA-Bw4-80I) protect against HIV progression to AIDS [71] |
|
|
|||
| Infectious disease | Enriched among individuals acquiring Dengue virus infection [95] | ||
|
|
|||
| Cancer | low affinity pairs are associated with the protection against relapse patients with AML after hematopoietic cell transplantation [26] | ||
|
|
|||
| Cancer | Enriched in patients with kidney cancer and non small cell lung carcinoma compared with healthy controls [112] | ||
|
| |||
| KIR3DL1 without HLA-Bw4 | Uneducated | Cancer | Protection against AML relapse after hematopoietic cell transplantation [26,83,97] |
|
|
|||
| Cancer | Improved overall survival and cancer control in patients treated with 3F8 antibody (Bw4-negative and weak binding pairs of KIR3DL1 + HLA-Bw4) [29,84,85] | ||
|
|
|||
| Infectious disease/cancer | Higher likelihood of hepatitis C-associated hepatocellular carcinoma [113] | ||
|
|
|||