International Immunology, Vol. 16, No. 2, pp. 197-204,
February 2004
© 2004 Japanese Society for Immunology
A species-specific determinant on ß2-microglobulin required for Ly49A recognition of its MHC class I ligand
1 Department of Integrated Biosciences, Graduate School of Frontier Sciences, the University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8562, Japan 2 Glyco-chain Functions Laboratory, Supra-biomolecular System Group, RIKEN Frontier Research System, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan
Correspondence to: N. Matsumoto; E-mail: nmatsu{at}k.u-tokyo.ac.jp
Transmitting editor: W. M. Yokoyama
The mouse inhibitory NK cell receptor Ly49A recognizes the mouse MHC class I molecule H-2Dk. The present study focuses on the species specificity of ß2-microglobulin (ß2m), an invariant component of MHC class I, in the interaction between Ly49A and H-2Dk. Transfection of the ß2m-defective mouse cell line R1E/TL8x.1 with human (h) ß2m induced cell-surface expression of H-2Dk, but failed to protect the cells from killing by Ly49A+ NK cells. In contrast, the cells transfected with mouse (m) ß2m were protected from killing by Ly49A+ NK cells. These data indicate that Ly49A distinguishes mß2m from hß2m when it recognizes the H-2Dk complexes. To identify the species-specific determinant of ß2m required for Ly49A recognition of H-2Dk, we prepared a panel of mß2m mutants and tested the H-2Dk that included each of the ß2m mutants for its capacity to engage Ly49A on NK cells. Ly49A failed to functionally recognize the H-2Dk that included the mß2m with K3R and Q29G mutations. Moreover, Ly49A was able to recognize the H-2Dk that included the hß2m with R3K and G29Q mutations. These data indicate that Lys3 and Gln29 consist of the central part of the species-specific determinant of ß2m required for Ly49A recognition of H-2Dk. The two residues are conserved in the mouse and the rat, in which NK cells use Ly49 family molecules as the receptors specific for MHC class I. These results suggest functional importance of ß2m in NK cell recognition of target cells.
Keywords: C-type lectin, cytotoxicity, inhibitory receptor, H-2 antigen, NK cell
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