Supplementary MaterialsData Supplement. clear as we learn more about the role of NK cells in cattle disease resistance and vaccination. Introduction Natural killer cells are a diverse lymphocyte population with fundamental roles in immunity, cancer, and reproduction (1). Extensive studies in humans and mice have shown that as part of the innate immune system, NK cells can recognize and kill transformed or infected cells, particularly those virally infected, and initiate subsequent immune responses through the release of cytokines. This cytokine release, in addition to direct interactions between NK cells and dendritic cells, also helps initiate the adaptive immune response mediated by B and T cells (2). In human reproduction, NK cells are also involved in forming the placenta through conversation with the extravillous trophoblast (1). These diverse NK cell functions are mediated by a plethora of activating and inhibitory cell surface receptors that recognize a diverse array of ligands. The balance of signals received from these Sophoretin kinase inhibitor receptors determines the activation status of an individual NK cell (3). NK cells express a wide range of receptors and other cell surface markers, some Mouse monoclonal antibody to c Jun. This gene is the putative transforming gene of avian sarcoma virus 17. It encodes a proteinwhich is highly similar to the viral protein, and which interacts directly with specific target DNAsequences to regulate gene expression. This gene is intronless and is mapped to 1p32-p31, achromosomal region involved in both translocations and deletions in human malignancies.[provided by RefSeq, Jul 2008] of which are expressed on other lymphocytes, whereas others are restricted to NK cells and some T cell subsets. This is particularly true of the inhibitory receptors, which are often members of large polymorphic gene families, and a majority of their ligands are the polymorphic MHC class Ia molecules (4). The conversation between NK cell receptors and MHC class I is usually fundamental not only for the recognition and subsequent activation against target cells but also Sophoretin kinase inhibitor for functional education and receptor repertoire development (5C7). This highly polymorphic system creates differential specificity and avidity between receptor and ligand pairs within populations (8). Avidity is also influenced by the peptide presented by the MHC class I, which can significantly alter the extent of NK cell inhibition (9, 10). A further diversity-generating mechanism is the variegated expression of receptors between individual NK cells, creating a differentially responsive cell population (5, 11, 12). The overall outcome is immune diversity created by the variable expression of polymorphic germline-encoded receptors, which can contribute to differential susceptibility to viral diseases in humans and mice. The extracellular domains of NK cell receptors that recognize MHC class Sophoretin kinase inhibitor I are either Ig-like or C-type lectin-like, and encoded within the leukocyte receptor complex (LRC) or NK complex (NKC), respectively. These gene complexes are located on different chromosomes in all mammals studied to date, and never on the same chromosome as the gene, which is usually nonfunctional. However, alongside a nonfunctional gene, the NKC contains a large gene expansion (16). Horses are the only nonrodent species known to have expanded the genes (17). The most extensive expansion described to date is in cattle, the only species known to have significantly expanded two MHC class I receptor gene families, the and haplotypesunlike those in humans and, to a large extent, micevary in the number of genes they contain (23). In humans the and genes are highly polymorphic but present on almost all haplotypes. diversity in Sophoretin kinase inhibitor cattle is usually generated by six relatively polymorphic classical genes, with between one and three present on any one haplotype. However, there is no evidence of one gene being more or less important for Ag presentation, although some genes appear dominant over others at restricting T cell responses to certain pathogens. This diversity presents significant challenges for the coevolution of germline-encoded MHC receptors that segregate independently. In cattle, this receptor ligand system has the potential to generate an enormous diversity of differentially responsive NK cells (23). The influence of this diversity on cattle NK cell function is usually yet to be comprehended. Cattle NK cells are defined by their expression of.