Novel SLA-DQ alleles and their recombinant molecules in xenogeneic stimulation of human T cells

Abstract

MHC class II antigens DR and DQ are essential for graft rejection both in allo- and xeno-transplantation. The antigens, especially the DQA and DQB gene-coencoded DQ molecules, are also involved in transplantation tolerance induced by activation of regulatory T cells. Here we report six novel DQ alleles from three properly inbred Chinese pig strains Gz, Bm and Yn. In our study, cDNA of swine leukocyte antigen (SLA)-DQA and -DQB were amplified by RT-PCR and sequenced for each strain. The ORF-containing SLA-DQA and -DQB genes are composed of 768 (or 765) and 786 nucleotides, encoding antigen molecules of 255 (or 254) and 261 amino acid residues, respectively. Sequences of both SLA-DQA and -DQB alleles showed disparities when compared either among the three pig strains or with available SLA data, which allows our novel alleles receiving their accession numbers from GenBank. The sequence analysis further revealed a phylogenic connection of our SLA-DQ alleles with SLA-DQ(c) haplotype. In addition, the homologies of MHC DQ or DQ-like molecules between Chinese pigs (SLA) and human (HLA) are higher than those between pigs and mice (H-2). By co-transfection of Bm pig DQA and DQB genes into L929 cells, the Bm-DQ heterodimer-expressed cells could effectively stimulate the human lymphoproliferation in presence of human APCs with a mean stimulation index (SI) 9.9+/-1.4. This functional assay indicated that our recombinant DQ antigens are capable of initiating human lymphoproliferation in a xeno-MLR.