Hybrid resistance in vitro. Possible role of both class I MHC and self peptides in determining the level of target cell sensitivity.
NK cells of F1 hybrids frequently exhibit an enhanced capacity to reject semisyngeneic parental bone marrow grafts, a phenomenon known as hybrid resistance. Attempts to define the mechanism whereby this occurs have been hampered by factors inherent in the use of an in vivo model, including the host immune response, microenvironment, immune cell trafficking patterns, and host irradiation. We show here that IL-2-activated NK cells (lymphokine-activated killer cells) can be used to establish an in vitro model that appears to mimic hybrid resistance. These effectors lyse parental lymphoblast targets in a pattern consistent with that observed in vivo, bear NK not T cell surface markers, and recognize target structures mapping to the MHC. By using this model, we then demonstrate that sensitivity to lysis of syngeneic F1 lymphoblasts can be augmented by exposing the targets to conditions that have been reported to permit the exchange of endogenous class I-bound self peptides for exogenous foreign sequences. These data suggest that both MHC class I molecules and the "self" peptides they bind contribute to determining the susceptibility of a target to hybrid resistance, and the data are discussed in the context of a model of NK recognition in which the sensitivity of a target to NK lysis is mediated by a complex of the class I MHC molecule and the self peptides it samples from the intracellular peptide pool.
Chadwick
B S
BS
Ontario Cancer Institute, Toronto, Canada.
Miller
R G
RG
D000818:Animals; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D006084:Graft Rejection; D006086:Graft vs Host Disease / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010455:Peptides / Q000502:physiology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D015395:Histocompatibility Antigens Class I; D007376:Interleukin-2; D010455:Peptides