Search

Nucleotide oligomerization domain 2 (NOD2) is a cytosolic pattern recognition receptor (PRR) that responds to muramyldipeptide (MDP), a component of peptidoglycans of gram positive and negative bacteria. NOD2 is involved in the modulation of signaling pathways for other PRRs, such as Toll-like receptors. Polymorphisms in NOD2 may evoke bowel disorders, and human Crohn's disease is significantly correlated with mis-sense insertion of the NOD2 gene. Such polymorphisms affecting ligand recognition in the NOD2 gene may also influence bowel flora in livestock, which is compromised by bowel diseases such as diarrhea. We investigated the functional variance of mis-sense polymorphisms in ligand recognition by porcine NOD2. The 1949T>C polymorphism, located in the region encoding the hinge domain of the molecule, notably diminished the functional response of porcine NOD2 to MDP. By comparison, the 2197A>C polymorphism, localized in the region corresponding to leucine-rich repeats, significantly augmented the response of porcine NOD2 to the ligand. The 1949C allele was rare among pig breeds, suggesting that this mutation is a disadvantage to pigs in their immune response to microbes. The 2197C allele, in contrast, was widely distributed among Western breeds and is most likely to be derived from wild boars in Asia. This is the first report of a causal relationship between molecular function and polymorphisms in PRRs in non-primate, non-rodent mammals. These findings suggest that the 2197C allele might confer an immune response advantage in modern pig breeds and may be a useful marker for breeding aimed at disease resistance in pigs.

To better understand the function and diversity of gammadelta T cells, we determined the genomic sequence encoding diversity (D) segments of the porcine TCR delta chain and its upstream regions, because pigs and other artiodactyls have relatively high proportions of gammadelta T cells. The revealed sequence contained 28 variable (V) alpha/delta segments, including 4 TRDV1 and at least 6 Ddelta segments, a much higher number than in humans and mice. All 6 of the Ddelta segments that had canonical recombination signal sequences were functionally utilized in expressed TCR delta chain genes. The multiplicity of Ddelta segments enabled the use of more than 3 Ddelta segments in a single functional TCR delta chain. The increased number of TCR delta segments was acquired by the duplication of the germline sequence, which occurred after the divergence of artiodactyls from primates and rodents. These data demonstrate that the pig is able to generate a highly diversified repertoire of TCR delta chain molecules.