The study of new SLA classical molecules in inbreeding Chinese Wuzhishan pig

Abstract

The pig may be used as an alternative organ donor source in the future. The Wuzhishan miniature pig (WZSP) is a Chinese inbred mini pig with the highest inbreeding coefficient and has been used in many biologic experiments. We studied the classical MHC molecules of WZSP to confirm its pure gene background and to provide information for xenotransplantation.

Methods: The classical class I (P1 and P14) and class II (DQA, DQB, DRA, and DRB) molecules were studied using RT-PCR. The products were cloned into a pGEM-T vector, respectively, sequenced and compared with related data for homology analysis.

Results: WZSP is highly homologous (>90%) with NIH miniature swine for class I and class II molecules amino acids in alpha-3 domain responsible for the binding of human T-cell CD8 were largely conserved; only two critical residues were altered. The critical residues of class I molecules recognized by human natural killer (NK) cells were completely different from humans. Furthermore, new class II molecules were homologous (>70%) with the Chinese south population in amino acids. The amino acids for binding to human CD4 were identical in DRB and showed only two differences in DRA.

Conclusions: WZSP bears new alleles in porcine MHC-relevant loci. We might alter residues of class I molecules to avoid killing by human NK cells. The striking similarities of DRB would make WZSP less likely in compatible in xeno-rejection. We can also alter the two residues of the DRA sequence to make WZSP a better model for xenotransplant research in China.