MHC class I characterization of Indonesian cynomolgus macaques

Abstract

Cynomolgus macaques (Macaca fascicularis) are quickly becoming a useful model for infectious disease and transplantation research. Even though cynomolgus macaques from different geographic regions are used for these studies, there has been limited characterization of full-length major histocompatibility complex (MHC) class I immunogenetics of distinct geographic populations. Here, we identified 48 MHC class I cDNA nucleotide sequences in eleven Indonesian cynomolgus macaques, including 41 novel Mafa-A and Mafa-B sequences. We found seven MHC class I sequences in Indonesian macaques that were identical to MHC class I sequences identified in Malaysian or Mauritian macaques. Sharing of nucleotide sequences between these geographically distinct populations is also consistent with the hypothesis that Indonesia was a source of the Mauritian macaque population. In addition, we found that the Indonesian cDNA sequence Mafa-B7601 is identical throughout its peptide binding domain to Mamu-B03, an allele that has been associated with control of Simian immunodeficiency virus (SIV) viremia in Indian rhesus macaques. Overall, a better understanding of the MHC class I alleles present in Indonesian cynomolgus macaques improves their value as a model for disease research, and it better defines the biogeography of cynomolgus macaques throughout Southeast Asia.

Fig. 1

Neighbor-joining tree of MHC class I cDNA sequences from cynomolgus macaques from Mauritius (M) and Indonesia (I). Numbers on the branches represent the percent of bootstrap samples supporting a given branch; only values ≥70% are shown

Fig. 2

Mafa-B*7601 and Mamu-B*03 share identical peptide-binding domains. Predicted amino acid translations of Mafa-B*7601, Mamu-B*03, and Mamu-B*08 were aligned with MegAlign software (DNASTAR, Madison, WI). Peptide-binding domains were predicted based on previous studies of MHC class I alleles in Indian rhesus macaques (Boyson et al. 1996)

Fig. 3

Mafa-B*4501 and Mafa-B*5101 are shared between Indonesian and Mauritian cynomolgus macaques. a PCR-SSP analysis of Mafa-B*4501 and Mafa-B*5101 in eight Indonesian cynomolgus macaques is shown. In parallel, primers based on sequences in exons 2 and 3 that are conserved in nearly all MHC class I alleles were used as a positive control to verify the cDNA integrity. Samples from H3/H3 and H1/H1 Mauritian cynomolgus macaques were used as positive and negative controls, respectively, for the amplification of Mafa-B*4501 and Mafa-B*5101. b Microsatellite analysis of the same eight Indonesian cynomolgus macaques and two control Mauritian macaques is shown. Microsatellite allele sizes matching those found in an H3/H3 homozygous animal are highlighted in blue. The names of the animals who express both Mafa-B*4501 and Mafa-B*5101 are also highlighted in blue