Allelic variation in theDR subregion of the canine major histocompatibility complex

Abstract

Allelic variation in the DR subregion of the canine major histocompatibility complex (DLA) has been analyzed by nucleic acid sequencing of cDNA clones of DRB genes amplified in vitro by the reverse transcriptase-polymerase chain reaction (RT-PCR). Sequence analysis of a panel of 19 homozygous typing cell dogs representing 12 different DLA-D types (defined by mixed leucocyte reaction) demonstrated the presence of one expressed DRB locus with at least nine distinct alleles in the dog. Unique DLA-DRB alleles were found in the DLA-D types Dw1, Dw3, Dw4, Dw8 (workshop assignments) and D4, D6, D7, D8, and D9 (Seattle assignments). In contrast, the DRB genes of the remaining three DLA-D types (D1, D10, and D16) were identical to those of Dw3/Dw4 (for D1), Dw8 (for D10), and D6 (for D16). The nucleotide sequences of all nine DLA-DRB alleles were typical of functional major histocompatibility complex (MHC) class II beta chains and contained three allelic hypervariable regions (HVRs) in the beta 1 domain at positions 8-16, 26-39, and 57-74. At each variable residue, two to five amino acid substitutions were found. The most polymorphic residues were located at positions 37 (with five amino acid substitutions), 11, 13, 28, and 71 (each with four substitutions). The DLA-DRB alleles had 96%-99% overall nucleotide sequence similarity and 93%-99% amino acid sequence similarity with each other. Cluster analysis of the nucleotide and predicted amino acid sequences subdivided the DLA-DRB alleles into three major allelic groups which may represent the canine counterparts of the supertypic groups described in man.

Molecular characterization of expressed DQA and DQB genes in the California sea lion ( Zalophus californianus )

“…If a yet undiscovered, more polymorphic class II MHC gene exists then these conclusions may be misleading. The most likely candidate genes are those encoding the DRa and DRp molecules, which have been shown to be polymorphic in some terrestrial carnivores (Sarmiento et al 1990;Wagner et al 1996;Yuhki and O'Brien 1997).…”

Structure and polymorphism of horse MHC class II DRB genes: convergent evolution in the antigen binding site

“…Figure 2 shows an alignment of the three horse amino acid sequences with DRB sequences of other mammalian species. The grouping of sequences across species indicates a high degree of sequence similarities between individual alleles of various species, in the ABS or parts thereof, as has been noted (Gustafsson et al 1990;Sarmiento et al 1990;Andersson et al 1991). This is particularly evident in 'hypervariable regions 1 and 2' (HVR 1 and 2), where, for example, three different species share the first seven ABS residues, i.e., human DRBl*1102 (Bell et al 1987), cow DRB3*4A , and horse DRB*I.…”

“…Despite the extensive polymorphism within species, a remarkable sharing of polymorphic sequence motifs has been observed between distantly related mammalian species (Gustafsson et al 1990;Sarmiento et al 1990;Andersson et al 1991;Lundberg and McDevitt 1992). Two possible mechanisms have been put forward to explain this phenomenon, i.e., convergent evolution and the maintenance of short ancestral sequence motifs.…”

“…This is particularly evident in 'hypervariable regions 1 and 2' (HVR 1 and 2), where, for example, three different species share the first seven ABS residues, i.e., human DRBl*1102 (Bell et al 1987), cow DRB3*4A , and horse DRB*I. Likewise, the second horse sequence, DRB*2, shares the same first seven ABS residues with another human (DRBl*1001) (Gustafsson et al 1984) and a dog DRB*Dw8 (Sarmiento et al 1990) sequence. In contrast, the number of shared residues, at the same positions, between the two horse alleles (DRBI*I and DRB1 *2) as well as between the two human alleles (DRBl*1102 and DRB*IO01) is only two of seven.…”

Effects of Genotype Matching of Feline Major Histocompatibility Complex (FLA) Class II DRB on Skin-allograft Transplantation in Cats.

“…However, it remains unknown what functions the expressed DRB genes have in cats. For the typing of transcribed genes, the reverse transcription (RT) method for synthesizing cDNA from RNA is applied [7,8,12,13]. In the present study, to confirm the effects of matching of FLA class II DRB genotype on transplantation immunity in cats, the durations of skin-allograft survival were compared among the cat pairs in which the DRB genotypes of cDNA were agreed or disagreed.…”