The Journal of Experimental Medicine
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Published 4 April 2005. doi:10.1084/jem.20050167
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 201, Number 7, 1145-1155
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ARTICLE

 Natural killer cell education in mice with single or multiple major histocompatibility complex class I molecules

Sofia Johansson1,2, Maria Johansson1,2, Eleftheria Rosmaraki1,2, Gustaf Vahlne1,2, Ramit Mehr2,3, Mali Salmon-Divon2,3, François Lemonnier4, Klas Kärre1,2, and Petter Höglund1,2

1 Microbiology and Tumor Biology Center, Karolinska Institutet, S-17177 Stockholm, Sweden
2 Strategic Research Center IRIS for studies of Integrative Recognition in the Immune System, Karolinska Institutet, S-17177 Stockholm, Sweden
3 Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel
4 Unité d'Immunité Cellulaire Antivirale, Institut Pasteur, 75715 Paris, France

CORRESPONDENCE Petter Höglund: petter.hoglund{at}mtc.ki.se

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 (Kb, Db, Dd, or Ld) 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 Kb or Dd conveyed strong rejection of MHC class I–deficient cells, whereas the expression of Db or Ld resulted in weaker responses. The educating impact of weak ligands (Db and Ld) was further attenuated by the introduction of additional MHC class I alleles, whereas strong ligands (Kb and Dd) 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.

Abbreviations used: CFSE, 5,6-carboxyfluorescein diacetate succinimidyl ester; DRI, down-regulating index; FI, fluorescence intensity.


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