Genetic Makeup of theDRRegion in Rhesus Macaques: Gene Content, Transcripts, and Pseudogenes

Abstract

In the human population, five major HLA-DRB haplotypes have been identified, whereas the situation in rhesus macaques (Macaca mulatta) is radically different. At least 30 Mamu-DRB region configurations, displaying polymorphism with regard to number and combination of DRB loci present per haplotype, have been characterized. Until now, Mamu-DRB region genes have been studied mainly by genomic sequencing of polymorphic exon 2 segments. However, relatively little is known about the expression status of these genes. To understand which exon 2 segments may represent functional genes, full-length cDNA analyses of -DRA and -DRB were initiated. In the course of the study, 11 cDRA alleles were identified, representing four distinct gene products. Amino acid replacements are confined to the leader peptide and cytoplasmatic tail, whereas residues of the α1 domain involved in peptide binding, are conserved between humans, chimpanzees, and rhesus macaques. Furthermore, from the 11 Mamu-DRB region configurations present in this panel, 28 cDRB alleles were isolated, constituting 12 distinct cDRA/cDRB configurations. Evidence is presented that a single configuration expresses maximally up to three -DRB genes. For some exon 2 DRB sequences, the corresponding transcripts could not be detected, rendering such alleles as probable pseudogenes. The full-length cDRA and cDRB sequences are necessary to construct Mhc class II tetramers, as well as transfectant cell lines. As the rhesus macaque is an important animal model in AIDS vaccine studies, the information provided in this communication is essential to define restriction elements and to monitor immune responses in SIV/simian human immunodeficiency virus-infected rhesus macaques.

Mhc class I haplotypes associated with survival time in simian immunodeficiency virus (SIV)-infected rhesus macaques

“…Mhc class I group 1 and group 2 configurations were also linked to Mhc class II haplotypes expressing two DRB genes, namely Mamu-DQB1*1801-DRB1*0303-DRB1*1007 and Mamu-DQB1*1811-DRB1*0406-DRB5*0301. 37 One of them (Mamu-DQB1*1801-DRB1*0303-DRB1*1007) was also linked to class I configurations associated with slow disease progression, including configuration 4. This finding indicates that Mhc class I genotypes have a much more marked influence upon disease progression than class II genotypes, thereby corroborating previous reports on HIV-infected humans 20 and SIV-infected macaques.…”

The Major Histocompatibility Complex Class II AllelesMamu-DRB1*1003and -DRB1*0306Are Enriched in a Cohort of Simian Immunodeficiency Virus-Infected Rhesus Macaque Elite Controllers

“…Both of these alleles were present at a frequency of 44% in the EC cohort but were present only at a frequency of less than 23% in the entire SIV-infected cohort (P values of 0.05 and 0.02 for Mamu-DRB1*0306 and Mamu-DRB1*1003, respectively) ( Table 3). Previously de Groot et al (9) showed that these two MHC-II alleles segregate together along with Mamu-DRA1*01041 as part of the same genetic configuration.…”

Reactivation by exon shuffling of a conservedHLA-DR3-like pseudogene segment in a New World primate species

“…PCR mixtures and conditions were as described in ref. 38, employing a commercially available Taq polymerase (Invitrogen). RT-PCR was performed directly on RNA by using the Qiagen OneStep RT-PCR kit according to the manufacturer's guidelines.…”