| First Author | Sentman CL | Year | 1994 |
| Journal | J Immunol | Volume | 153 |
| Issue | 12 | Pages | 5482-90 |
| PubMed ID | 7989750 | Mgi Jnum | J:180044 |
| Mgi Id | MGI:5305044 | Doi | 10.4049/jimmunol.153.12.5482 |
| Citation | Sentman CL, et al. (1994) H-2 allele-specific protection from NK cell lysis in vitro for lymphoblasts but not tumor targets. Protection mediated by alpha 1/alpha 2 domains. J Immunol 153(12):5482-90 |
| abstractText | In vivo murine NK cells are known to mediate graft rejection in allogenic as well as in "F1 anti-parental" situations. We have studied an in vitro system based on rIL-2-activated spleen cells and Con A lymphoblast targets in relation to the genetics of F1 hybrid resistance and NK cell activity. We demonstrate that NK cells in this in vitro model are regulated by MHC class I genes in an allele-specific manner at the level of the effector and the target. Using rIL-2-activated effector cells from nude C57BL/6 (B6) and BALB/c mice, we observed no killing of MHC syngeneic lymphoblasts. However, B6 as well as BALB/c lymphoblasts were killed by effector cells from allogeneic nude mice as well as by cells from (BALB/c x B6)F1 hybrids. Experiments that used D8 mice (which carry an H-2Dd transgene on B6 background) and beta 2-m-/- mice demonstrated a direct role for MHC class I molecules at the effector as well as at the target cell level: H-2Dd transgenic effector cells with the typical NK phenotype 3A4+/CD8- killed B6 blasts, but expression of the corresponding H-2Dd transgene in the target lymphoblasts protected them from killing. By using transgenic mice carrying exon shuffled MHC class I transgenes, the protective effect of the H-2Dd molecule was mapped to the alpha 1/alpha 2 domains. MHC class I-deficient lymphoblasts from beta 2-m-/- mice were killed by effectors from all strains of mice, including those matched for MHC. The H-2 class I allele-specific protection in this in vitro assay was observed for lymphoblasts but not for tumor cells, despite the fact that these tumor cells are protected in an allele-specific manner in vivo. |
