Characterization of the major histocompatibility complex class II DOB, DPB1, and DQB1 alleles in cynomolgus macaques of Vietnamese origin

Abstract

Major histocompatibility complex (MHC) molecules play an important role in the susceptibility and/or resistance to many diseases. To gain an insight into the MHC background and to facilitate the experimental use of cynomolgus macaques, the second exon of the MhcMafa-DOB, -DPB1, and -DQB1 genes from 143 cynomolgus macaques were characterized by cloning to sequencing. A total of 16 Mafa-DOB, 16 Mafa-DPB1, and 34 Mafa-DQB1 alleles were identified, which revealed limited, moderate, and marked allelic polymorphism at DOB, DPB1, and DQB1, respectively, in a cohort of cynomolgus macaques of Vietnamese origin. In addition, 16 Mafa-DOB, 5 Mafa-DPB1, and 8 Mafa-DQB1 alleles represented novel sequences that had not been reported in earlier studies. Almost of the sequences detected at the DOB and DQB1 locus in the present study belonged to DOB*01 (100%) and DQB1*06 (62%) lineages, respectively. Interestingly, four, three, and one high-frequency alleles were detected at Mafa-DOB, -DPB1, and -DQB1, respectively, in this monkeys. The alleles with the highest frequency among these monkeys were Mafa-DOB*010102, Mafa-DPB1*13, and Mafa-DQB1*0616, and these were found in 33 (25.6%) of 129 monkeys, 32 (31.37%) of 102 monkeys, and 30 (31%) of 143 monkeys, respectively. The high-frequency alleles may represent high priority targets for additional characterization of immune function. We also carried out evolutionary and population analyses using these sequences to reveal population-specific alleles. This information will not only promote the understanding of MHC diversity and polymorphism in the cynomolgus macaque but will also increase the value of this species as a model for biomedical research.

Fig. 1

Alignment of the deduced amino acid sequences of the second exon of 16 cynomolgus macaque MhcMafa-DOB alleles and 6 human HLA-DOB alleles

Fig. 2

Alignment of the deduced amino acid sequences of the second exon of 52 Mafa-DPB1, 33 Mamu-DPB1, and 18 HLA-DPB1 sequences. Five novel alleles were listed in the middle frame; previously reported alleles also detected in this study were indicated by an underline

Fig. 3

Alignment of the deduced amino acid sequences of the second exon of 47 Mafa-DQB1, 23 Mamu-DQB1, and 11 HLA-DQB1 sequences. Eight novel alleles were listed in the middle frame, 26 sequences common to the earlier studies were listed in the over frame, and other alleles not detected in this study were listed under the frame

Fig. 4

Phylogenetic tree of 5 Mafa-DOB, 1 HLA-DOB, and 1 BoLA-DOB amino acid sequences

Fig. 5

Phylogenetic tree of 52 Mafa-DPB1, 33 Mamu-DPB1, and 18 HLA-DPB1 amino acid sequences. Novel alleles identified in this study were shown with a solid round spot; previously reported alleles also detected in this study were shown with a solid triangle

Fig. 6

Phylogenetic tree of 47 Mafa-DQB1, 23 Mamu-DQB1, and 11HLA-DQB1 amino acid sequences. Novel alleles identified in this study were shown with a solid round spot and boldface, previously reported alleles also detected in this study were shown with a solid triangle; alleles not detected in this study were indicated by underline