Novel SLA class I alleles of Chinese pig strains and their significance in xenotransplantation

• Published in: Cell research Vol. 13; no. 4; pp. 285 - 294
• Main Authors: Chen, Fu Xiang, Tang, Jun, Li, Ning Li, Shen, Bo Hua, Zhou, Yun, Xie, Jin, Chou, Kuang Yen
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.08.2003; The Oriental Hospital, Tongji University,Shanghai 200120%Shanghai Institute of Immunology, Shanghai Second Medical University, Shanghai 200025, China
• Subjects: Alleles; Amino Acid Sequence; Amino acids; Animals; Base Sequence; CD8 Antigens - immunology; CD8 Antigens - metabolism; Cell Line; Genes, MHC Class I; Graft Rejection; Histocompatibility Antigens Class I - immunology; Histocompatibility Antigens Class I - metabolism; Humans; Killer Cells, Natural - metabolism; Mice; Molecular Sequence Data; Receptors, Immunologic - metabolism; Receptors, KIR; Residues; Sequence Alignment; SLA; Sus scrofa; Swine; Swine - genetics; Swine - immunology; T-Lymphocytes - cytology; T-Lymphocytes - physiology; Transplantation, Heterologous - immunology; 中国猪; 等位基因; swine leukocyte antigens (SLA); Chinese pig train; xenotransplantation; killer cell inhibitory receptor (KIR); CD8 coreceptor
• ISSN: 1001-0602; 1748-7838
• DOI: 10.1038/sj.cr.7290173

To lay background for studying rejection mechanisms in xenotransplantation and developing the strate-gies for intervention, class I genes of swine leukocyte antigens (SLA) of three Chinese pig strains Bm, Gz and Yn were cloned and sequenced. The cDNA of the class I loci P1 and P14 were amplified by RT-PCR and subjected to insert into sequencing vectors. All six allelic sequences we examined, each two for one Chinese strain, are not identical to those reported, which allows these novel sequences receiving their ac-cession numbers AY102467- AY102472 from GenBank. This study further reveals that the homologies of MHC class I genes in their primary structures and the deduced amino acids between Chinese pigs (SLA) and human (HLA-A^*0201) are better than those between pigs and mice (H-2D^b/H-2K^b). The comparison also indicates that the amino acid residues critical for recognition by human KIRs are altered in the swine class I molecules. The amino acids responsible for binding human CD8 coreceptor are largely conserved although there are two critical residues substituted. A functional test indicated that the human T cells specific for the prokaryotically expressed SLA Plprotein could respond quite well in vitro to the class I-positive swine chon-drocytes and PBMCs in presence of human APCs. This implies that, due to the substitution of two critical residues, the inaccessibility of human CD8 coreceptor to swine class I molecule might be contributable to the indirect pathway that the human T cells have to use for recognizing the SLA class I xenogeneic antigens.