| The success of organ transplantation has led to an ever-increasing shortfall between the demand for organs and the supply in late 40 years. This has given more chances to extensive investigation of the possible use of animals, especially the pigs, as organ donors.Hyperacute xeno-rejection was overcome through inhibiting the activation of the complement system. The acute vascular rejection and acute cellular rejection become more and more important in xenotransplantation rejection research. The new focus were Swine Leukocyte Antigen (SLA) and the mechanisms of antibody dependent cell mediated cytotoxicity (ADCC) induced by natural killer cells (NK) as well as the rejection mechanism induced by CD4+ and CD8+ T cells. The NK cells cytotoxicity to porcine endothelial cell (PEC) is the first stage and also the most important point in the delayed xeno-rejection. NK cells possess granules containing perform and granzyme that are released upon activation to mediate cytotoxicity in target PECsSequence Analysis of Classical Swine Leukocyte Antigens (SLA) Class I and Class II Molecules in Chinese PigsForeign research groups analyzed some SLA antigen systems of different pig strains since 1980s companied with progress of molecular technology. They have provided some useful evidences to explain the MHC restriction in recognition process by human immune cells. China is rich in swine resources and has more than 100 natural strains and most of them have stale characteristics.To screen a proper pig strain for xenograft, Hubei White Pigs (HBWP), inbred Wuzhishan miniature pigs (WZSP) and inbred Yunnan Bana miniature pigs (BMI) were taken as the subjects. The classical SLA class I molecules (P1 and P14) and class II molecules (DQA DQB DRA DRB) were investigated by reverse transcription polymerase chain reaction (RT-PCR) to obtain cDNA products. The purified products were sequenced and compared with the data of NIH miniature pigs as well as those relevant to high frequency genes of HLA in Genbank for homology analysis and some other related comparisons.The findings indicated that three Chinese pigs are highly homologous (>90%) with the inbred NIH miniature swine in characterization of porcine MHC classical class I and class II molecules. While, the obtained DRA sequence is completely same and is confirmed that DRA molecule is highly conserved in the porcine genes. So, the other sequences obtained are the new alleles in relevant loci (P1, P14, DQA, DQB and DRB). The homologous comparison with the HLA-A*0201 was about 63% in amino acid level. The greatest degree of polymorphism is within the a1 and a2 domains, while the others are highly conserved. The various series SLA may have less difference in this binding domain. The amino acids in a2 and a3 domains those were responsible for binding with human CD8 to MHC class I were largely conserved, only two critical residues were altered, which were a Ala-Val change at position 223 and a Ala-Lys change at position 235. And, correlative comparison of the amino acids for binding of human CD4 to MHC class II revealed that only two amino acids responsible for binding of CD4 were altered, a Arg-Gly change at position 125 and the other change Val-Ile at position 129. Therefore, the key residues of new DRB for binding of CD4 are the same as those in HLA-DRB*09012 absolutely. There was no similar report in related research before. The high similarity of SLA class I and II molecules show that they would bind with human CD8 or CD4 molecules and play some similar roles. None of the binding sequences responsible for killer inhibitory receptors were present in the porcine molecules in this study. It would result great killing of pig cells by human NK cells in xeno-rejection.In a word, SLA molecules of inbred WZSP and BMI are highly homologous with HLA relevant molecules. And, they have some specific and stable mutation characteristic. However, there are no certain answer to say these two inbred strains would be the best animal model in future porcine-human xenotransplantation just according to l... |
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