Class I MHC-Binding characteristics of the 129/J Ly49 repertoire

The Ly49 family of NK cell receptors and its MHC-binding characteristics ha ve only been well characterized in C57BL/6 (B6) mice. Previous studies have shown that 129/J mice express unique Ly49 genes that are not found in the B6 strain. Screening of a 129/J cDNA library led to the discovery of 10 dis tinct full-length Ly49-related coding sequences (Ly49c, g, i, o, p, r, s, t , u, and v). Although 129/J mice share identical class I MHC (K-b and D-b) transcripts with B6 mice, only one Ly49 is identical in the two strains (Ly 49E). In addition to the previously characterized Ly49P, two new activating Ly49 proteins were discovered, Ly49R and U. The MHC specificity of the tot al 129J Ly49 repertoire was evaluated with soluble class I MHC tetramers an d found to be distinct compared with the B6 Ly49 repertoire. Ly49V bound to many types of class I MHC, suggesting that Ly49V(+) NK cells may monitor h ost cells for a global down-regulation in MHC levels. An activating recepto r, Ly49R, was shown to bind soluble class I molecules to a moderate degree, a result not previously observed for other activating Ly49 proteins. Furth ermore, tetramer-binding results were confirmed functionally with cytotoxic ity assays using sorted 129/J NK cells. This study shows that the Ly49 repe rtoire and its MHC-binding characteristics can be very different among inbr ed mouse strains. Ly49 divergence should be considered when using 129-deriv ed embryonic stern cells for the production of gene-targeted mice, especial ly when an immune or NK-derived phenotype is under scrutiny. The Journal of Immunology, 2001.