MHC class I mosaic mice reveal insights into control of Ly49C inhibitory receptor expression in NK cells.
We have analyzed lymphocyte development in natural MHC class I chimeric mice, generated through a transgenic approach in beta2-microglobulin (beta2m)-/- mice. In these mice, MHC class I+ cells coexist with an equal proportion of MHC class I-deficient cells. These MHC class I mosaic mice had normal numbers of CD8+ T cells, which had a target cell specificity similar to that of wild-type mice. Consequently, the mice did not develop any signs of autoimmunity. They also had normal numbers of NK cells. This allowed an examination of the MHC class I influence on the expression of the Ly49C inhibitory receptor on NK cells. This receptor binds to H-2Kb. It is expressed at low levels on NK cells in wild-type mice of the H-2b haplotype, but at markedly higher levels on NK cells in beta2m-/- mice and other strains of mice lacking expression of H-2Kb. Relatively little is known about how MHC class I molecules affect expression of the Ly49 receptors. Through the analysis of the present MHC class I mosaic mice, we demonstrate that the expression levels of Ly49C on NK cells is a consequence not only of MHC class I expression in the environment, but also of the expression of MHC class I molecules by the NK cells themselves. These findings are discussed in relation to the biological role of the calibration of the Ly49 inhibitory receptor expression in relation to self-MHC class I.
Andersson
M
M
Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden.
Freland
S
S
Johansson
M H
MH
Wallin
R
R
Sandberg
J K
JK
Chambers
B J
BJ
Christensson
B
B
Lendahl
U
U
Lemieux
S
S
Salcedo
M
M
Ljunggren
H G
HG
D000818:Animals; D000950:Antigens, Ly; D002678:Chimera / Q000276:immunology*; D005786:Gene Expression Regulation; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology; D006239:Haplotypes; D064532:Histocompatibility Antigen H-2D; D007694:Killer Cells, Natural / Q000378:metabolism*; D037181:Lectins, C-Type; D018655:Lymphocyte Count; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D055650:NK Cell Lectin-Like Receptor Subfamily A; D055630:Receptors, NK Cell Lectin-Like; D015854:Up-Regulation; D001613:beta 2-Microglobulin / Q000172:deficiency / Q000235:genetics
D000950:Antigens, Ly; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D064532:Histocompatibility Antigen H-2D; C527091:Klra3 protein, mouse; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D055650:NK Cell Lectin-Like Receptor Subfamily A; D055630:Receptors, NK Cell Lectin-Like; D001613:beta 2-Microglobulin