Cloning and characterization of a novel activating Ly49 closely related toLy49A

The majority of the known Ly49 family members have been isolated from eithe r C57BL/6 (B6) or BALB/c mice, Interestingly, the anti-Ly49 Ab reactivities observed in 129/J mice are different from those of B6 mice. Furthermore, i mmunoprecipitation of 129/J NK cell lysates with YE1/32 and YE1/48, Abs spe cific for the inhibitory Ly49A in B6, resulted in detection of the activati on-associated DAP12 molecule. These results indicated a need for a more det ailed study of this strain. Therefore, cloning strategy was devised to isol ate Ly49 cDNAs from 129/J mice. An immunoreceptor tyrosine-based inhibitory motif-containing, Ly49D-related clone was discovered that we have named Ly 49O, and one immunoreceptor tyrosine-based inhibitory motif-lacking, Ly49A- related clone was discovered that we have named Ly49P. No anti-Ly49 mAb rea cted with Ly49O, whereas the molecule encoded by the Ly49P cDNA was found t o react with YE1/32 and YE1/48. Ly49P was found to associate with mouse DAP 12, and Ah-mediated cross-linking of Ly49P resulted in mouse DAP12 phosphor ylation and Ca2+ mobilization, indicating that Ly49P is a competent activat ion receptor. Ly49P, therefore, represents a novel member of the Ly49 activ ating receptor subfamily.