Levels of Ly-49 receptor expression are determined by the frequency of interactions with MHC ligands: Evidence against receptor calibration to a "useful" level

Ly-49 receptor expression was studied in NK cells that developed in fully M HC-mismatched mixed bone marrow chimeras, in which host and donor MHC ligan ds were expressed solely on various proportions of hemopoietic cells or on both hemopoietic and nonhemopoietic cells. When hemopoietic cells were the only source of MHC ligand, a strong correlation between the level of down-r egulation of Ly-49A, Ly-49C, and Ly-49G2 and the number of hemopoietic cell s expressing their MHC ligands was observed on both donor and host NK cells . In some animals with low levels of donor hemopoietic chimerism, NK cells of donor origin expressed Ly-49 receptors at higher levels than was observe d in normal mice of the same strain. This unexpected observation is inconsi stent with the receptor calibration theory, which states that expression of Ly-49 inhibitory receptors is calibrated to an optimal level to maintain a n Mt cell repertoire that is sensitive to perturbations in normal class I l igand expression, Our data suggest a model in which Ly-49 receptors down-mo dulate in accordance with the frequency of their interactions with ligand-b earing cells, rather than a model in which these receptors calibrate to a s pecific "useful" level in response to ligands present in their environment.