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The Rat RT1-A1^c MHC Molecule Is a Xenogeneic Ligand Recognized by the Mouse Activating Ly-49W and Inhibitory Ly-49G Receptors¹

Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada

Mouse Ly-49 receptors are known to recognize xenogeneic ligands from hamster and rat. However, until now, there has been no description of a specific rat xenogeneic ligand for any mouse Ly-49 receptor. In this report, we identify RT1-A1^c, a rat classical class I MHC molecule, as a ligand for the Ly-49G^BALB/c inhibitory receptor and the closely related activating receptor, Ly-49W. Xenogeneic class I recognition of targets from PVG but not DA strain rats was mapped to the classical region of the RT1^c haplotype by using Con A blasts from RT1^c/RT1^av1 intra-MHC recombinant rats as targets for RNK-16 cells expressing either Ly-49W or Ly-49G^BALB/c receptors. Individual expression of class I molecules from PVG and DA rat strains in YB2/0 target cells demonstrate the xenogeneic recognition to be allele specific, because other class I molecules of the RT1^c haplotype, RT1-A2^c and RT1-U2^c, and a classical class I molecule encoded by the RT1^av1 haplotype, RT1-A^a, are not recognized by Ly-49W and -G^BALB/c. Furthermore, specificity for RT1-A^c can be transferred from Ly-49W to Ly-49P, which is normally unable to recognize RT1-A^c, by substitution of three residues shared by Ly-49W and -G^BALB/c but not Ly-49P. These residues are located in the Ly-49 4–5 loop, which can determine class I allele specificity in mouse Ly-49 receptor interactions with mouse class I ligands, suggesting that mouse Ly-49 recognition of rat class I molecules follows similar principles of interaction. These findings have implications for xenotransplantation studies and for discerning Ly-49 recognition motifs present in MHC molecules.

This article has been cited by other articles:

				K. J. Lavender, H. H. Chau, and K. P. Kane Distinctive Interactions at Multiple Site 2 Subsites by Allele-Specific Rat and Mouse Ly49 Determine Functional Binding and Class I MHC Specificity J. Immunol., November 15, 2007; 179(10): 6856 - 6866. [Abstract] [Full Text] [PDF]

				K. J. Lavender and K. P. Kane Cross-Species Dependence of Ly49 Recognition on the Supertype Defining B-Pocket of a Class I MHC Molecule J. Immunol., December 15, 2006; 177(12): 8578 - 8586. [Abstract] [Full Text] [PDF]