The study of new SLA class I molecules in Hubei White swines
Introduction The swine leukocyte antigen complex is critical in elucidation of the mechanism of the immune response in xenorejection. In China, there are rich in swine resources and the natural stains of swine are more than 100. It may provide the possibility to find a stain of proper pig as a universal donor for human xenotransplantation. In this study, we investigated a special Chinese Hubei White Pig, and characterize the polymorphism of its SLA class I molecules.
Materials and methods Muscle tissues of 12 pigs were collected freshly. Total RNA was extracted from these samples, respectively, using TRIzol reagent, and then got cDNA by RT-PCR. The products were purified and sequenced. The sequencing results were compared with genebank database for polymorphism and homology analysis.
Results Ten P1 gene sequences and nine of P14 were obtained from the Hubei White pigs. The sequences are highly homologous with those of the NIH miniswine. And compared with the highest frequency allele of the HLA class I gene in the south China population, HLA-A*0201, we found the homology is also above 70%, especially in those critical residues for antigen binding sites. Its greatest degree of polymorphism are within the α-1 and α-2 domains of the class I heavy chain, while the others are highly conserved. Amino acids in the α-2 and α-3 domains responsible for binding of human CD8 to MHC class I were largely conserved in the porcine genes, but two of the critical residues were altered. Comparison of sequences recognized by human NK cell receptors revealed that the residues critical for recognition by these receptors were completely different in the porcine genes.
Conclusion They are the new alleles in P1 and P14 loci. From the results, we may conclude that the mechanism of the recognition between the human and the targeted porcine cells is varying in the different stages in pig-human xenotransplantation.