Natural killer cell education in mice with single or multiple major histocompatibility complex class I molecules.
The ability of murine NK cells to reject cells lacking self MHC class I expression results from an in vivo education process. To study the impact of individual MHC class I alleles on this process, we generated mice expressing single MHC class I alleles (K(b), D(b), D(d), or L(d)) or combinations of two or more alleles. All single MHC class I mice rejected MHC class I-deficient cells in an NK cell-dependent way. Expression of K(b) or D(d) conveyed strong rejection of MHC class I-deficient cells, whereas the expression of D(b) or L(d) resulted in weaker responses. The educating impact of weak ligands (D(b) and L(d)) was further attenuated by the introduction of additional MHC class I alleles, whereas strong ligands (K(b) and D(d)) maintained their educating impact under such conditions. An analysis of activating and inhibitory receptors in single MHC class I mice suggested that the educating impact of a given MHC class I molecule was controlled both by the number of NK cells affected and by the strength of each MHC class I-Ly49 receptor interaction, indicating that NK cell education may be regulated by a combination of qualitative and quantitative events.
Johansson
Sofia
S
Microbiology and Tumor Biology Center, Karolinska Institutet, S-17177 Stockholm, Sweden.
Johansson
Maria
M
Rosmaraki
Eleftheria
E
Vahlne
Gustaf
G
Mehr
Ramit
R
Salmon-Divon
Mali
M
Lemonnier
François
F
Kärre
Klas
K
Höglund
Petter
P
D000483:Alleles; D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D015536:Down-Regulation; D005434:Flow Cytometry; D005452:Fluoresceins; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000378:metabolism*; D037181:Lectins, C-Type; D051379:Mice; D008822:Mice, Transgenic; D011971:Receptors, Immunologic / Q000378:metabolism*; D055630:Receptors, NK Cell Lectin-Like; D055607:Receptors, Natural Killer Cell; D017634:Self Tolerance / Q000235:genetics* / Q000276:immunology; D013388:Succinimides
C087165:5-(6)-carboxyfluorescein diacetate succinimidyl ester; D000950:Antigens, Ly; D005452:Fluoresceins; D015395:Histocompatibility Antigens Class I; D037181:Lectins, C-Type; D011971:Receptors, Immunologic; D055630:Receptors, NK Cell Lectin-Like; D055607:Receptors, Natural Killer Cell; D013388:Succinimides