Ly49A allelic variation and MHC class I specificity

The Ly49 family of natural killer (NK) cell receptors is encoded by a polyg enic genetic locus. Allelic forms have been described and their expression appears to be regulated. The best-characterized Ly49 molecule, the C57BL/6 form of Ly49A, is an NK cell inhibitory receptor that binds H2D(d). To dete rmine whether differences between Ly49a alleles may have functional consequ ences, allelic variants of Ly49a were cloned from several inbred mouse stra ins. Stable transfectants expressing each Ly49a allelic variant were genera ted and tested for reactivity with a panel of monoclonal antibodies (mAbs A 1, JR9.318, YE1/32, and YE1/48) that recognize the C57BL/6 form of Ly49A. B inding to H2Dd was also assessed using fluorescently labeled H2D(d) tetrame rs. Furthermore, cytotoxicity assays were performed using anti-Ly49A mAb-se parated interleukin-2-activated NK cells. We show that despite binding to f luorescently labeled H2Dd tetramers, the Ly49A(+) NK cells from representat ive mouse strains displayed significantly different degrees of inhibition w ith H2D(d) targets. These results can be interpreted in the li-ht of recent structural data on the Ly49A-H2D(d) complex. Thus, the Ly49 family display s functionally significant allelic polymorphism which adds to the repertoir e of NK cell receptors.