The major histocompatibility complex in swine

Abstract

In swine, the major histocompatibility complex (Mhc) or swine leukocyte antigen (SLA) is located on chromosome 7 and divided by the centromere. Thus, the telomeric class I and more centromeric class III regions are located on the p arm and the class II region is located on the q arm. The SLA region spans about 2 Mb, in which more than 70 genes have so far been characterized. Despite its division by the centromere, the spatial relationships between the genes in the class II and class III regions, and between the well-conserved non-class I genes of the class I region, are similar to those found in the human HLA complex. On the other hand, no orthologous relationships have been found between the Mhc class I genes in man and swine. In swine, the 12 SLA class I sequences constitute two distinct clusters. One cluster comprises six classical class I-related sequences, while the other comprises five class I-distantly related sequences including two swine homologous genes of the HLA Mhc class I chain-related gene (MIC) sequence family. The number of functional SLA classical class I genes, as defined by serology, probably varies from one to four, depending on the haplotype. Some of the SLA class I-distantly related sequences are clearly transcribed. As regards the SLA class II genes, some of them clearly code for at least one functional SLA-DR and one SLA-DQ heterodimer product, but none code for any DP product. The amino acid alignment of the variable domains of 33 SLA classical class I chains, and 62 DR beta and 20 DQ beta chains confirmed the exceptionally polymorphic pattern of these polypeptides. Among the class II genes, the genes are either monomorphic, like the DRA gene, or oligomorphic, like the DQA genes. In contrast, the DRB and DQB genes display considerable polymorphism, which seems more marked in DRB than DQB genes.

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

“…SLA molecules are encoded by a group of tightly linked genes located on 7p1.1 and 7q1.1 of pig chromosome. The main loci of SLA class I genes are P1 and P14 [8,9]. China is rich in natural resources of pigs.…”

The porcine Major Histocompatibility Complex and related paralogous regions: a review

“…The SLA-7 gene has been shown to give rise to a transcript in cultured swine fibroblasts [8], although neither its expression in these cells and other tissues nor its polymorphism has yet been studied. The transcription, expression and polymorphism of the SLA-8 gene must also be studied.…”

“…While the single swine DRA gene is monomorphic, the DQA gene and above all the DQB and DRB genes are polymorphic. This polymorphism, revealed by direct nucleotide sequencing, is essentially concentrated in the first domain (second exon) [8], in a region which forms the floor and wall of the peptide-binding groove. The serology of the SLA class II molecules has not been used routinely, mainly because of the existence of a wide range of class II cross-reactions among the classical reagents.…”

“…All Ia genes code for a polymorphic heavy glycoprotein chain of about 45 kiloDaltons (kDa) which binds non-covalently to the monomorphic β2-microglobulin at the cell membrane [35]. The polymorphism of swine SLA class Ia genes corresponds to amino acid substitutions in positions involved either in fixing the foreign peptides or in establishing direct contact with the T -cell-receptor [8]. This polymorphism is located in the extracellular α1 and α2 domains of SLA class I genes, and is almost perfectly superimposable on those of the human HLA class Ia sequences.…”

“…Numerous single-copy or anchor genes present throughout this region constitute a framework which has been well conserved during the evolution of the mammalian MHC region [1,8,42].…”