Ly-49 receptors are lectin-like type II transmembrane disulfide-bonded homodimers expressed on natural killer (NK) cells and some T-cell subsets. Cell-mediated cytotoxicity and release of cytokines/chemokines are functions regulated by Ly-49 recognition of class I major histocompatibility complex proteins (MHC-I) or virus-encoded MHC-like product(s). Here we examine diversity and conservation found within the Ly-49 gene family and explore the importance of polymorphism in Ly-49 receptor expression, specificity, and function. Several parallels are evident between Ly-49 receptors in rodents and killer Ig-related (KIR) receptors in humans, including receptor gene amplification and diversification, expression patterns, MHC-I specificity, shared signaling, and ultimate effects on NK-cell functions. These similarities suggest that insights gained in defining Ly-49 receptor functions in small animal models could have direct relevance to existing clinical challenges where there may be opportunities to manipulate human NK cells and KIR receptors for therapeutic benefit.
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