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Levels of Ly-49 Receptor Expression Are Determined by the Frequency of Interactions with MHC Ligands: Evidence Against Receptor Calibration to a "Useful" Level¹

Jennifer O. Manilay^*,, Gerald L. Waneck^, and Megan Sykes^2,*,

^* Bone Marrow Transplantation Section, Laboratory of Molecular and Cellular Immunology, and Transplantation Biology Research Center, Surgical Service, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02129

Ly-49 receptor expression was studied in NK cells that developed in fully MHC-mismatched mixed bone marrow chimeras, in which host and donor MHC ligands 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-regulation of Ly-49A, Ly-49C, and Ly-49G2 and the number of hemopoietic cells 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 observed in normal mice of the same strain. This unexpected observation is inconsistent with the receptor calibration theory, which states that expression of Ly-49 inhibitory receptors is calibrated to an optimal level to maintain an NK cell repertoire that is sensitive to perturbations in normal class I ligand expression. Our data suggest a model in which Ly-49 receptors down-modulate in accordance with the frequency of their interactions with ligand-bearing cells, rather than a model in which these receptors calibrate to a specific "useful" level in response to ligands present in their environment.

This article has been cited by other articles:

				Y. Zhao, H. Ohdan, J. O. Manilay, and M. Sykes NK Cell Tolerance in Mixed Allogeneic Chimeras J. Immunol., June 1, 2003; 170(11): 5398 - 5405. [Abstract] [Full Text] [PDF]

				L. Fahlen, U. Lendahl, and C. L. Sentman MHC Class I-Ly49 Interactions Shape the Ly49 Repertoire on Murine NK Cells J. Immunol., June 1, 2001; 166(11): 6585 - 6592. [Abstract] [Full Text] [PDF]