The repertoire of MHC class I genes in the common marmoset: evidence for functional plasticity
In humans, the classical antigen presentation function of major histocompatibility complex (MHC) class I molecules is controlled by the human leukocyte antigen HLA -A, HLA-B and HLA-C loci. A similar observation has been made for great apes and Old World monkey species. In contrast, a New World monkey species such as the cotton-top tamarin (Saguinus oedipus) appears to employ the G locus for its classical antigen presentation function. At present, little is known about the classical MHC class I repertoire of the common marmoset (Callithrix jacchus), another New World monkey that is widely used in biomedical research. In the present population study, no evidence has been found for abundant transcription of classical I class genes. However, in each common marmoset, four to seven different G-like alleles were detected, suggesting that the ancestral locus has been subject to expansion. Segregation studies provided evidence for at least two G-like genes present per haplotype, which are transcribed by a variety of cell types. The alleles of these Caja-G genes cluster in separate lineages, suggesting that the loci diversified considerably after duplication. Phylogenetic analyses of the introns confirm that the Caja-G loci cluster in the vicinity of HLA-G, indicating that both genes shared an ancestor. In contrast to HLA-G, Caja-G shows considerable polymorphism at the peptide-binding sites. This observation, together with the lack of detectable transcripts of A and B-like genes, indicates that Caja-G genes have taken over the function of classical class I genes. These data highlight the extreme plasticity of the MHC class I gene system.
KeywordsNonhuman primates MHC New World monkey Common marmoset Evolution
The authors would like to thank Ms. Donna Devine for editing the manuscript and Henk van Westbroek for preparing the figures. The research was financed by the Biomedical Primate Research Centre.
- de Groot NG, Otting N, Robinson J, Blancher A, Lafont BA, Marsh SG, O’Connor DH, Shiina T, Walter L, Watkins DI, Bontrop RE (2012) Nomenclature report on the major histocompatibility complex genes and alleles of Great Ape, Old and New World monkey species. Immunogenetics 64:615–631PubMedCrossRefGoogle Scholar
- Jagessar SA, Heijmans N, Blezer EL, Bauer J, Blokhuis JH, Wubben JA, Drijfhout JW, van den Elsen PJ, Laman JD, Hart BA (2012) Unravelling the T-cell-mediated autoimmune attack on CNS myelin in a new primate EAE model induced with MOG34-56 peptide in incomplete adjuvant. Eur J Immunol 42:217–227PubMedCrossRefGoogle Scholar
- Marsh SG, Albert ED, Bodmer WF, Bontrop RE, Dupont B, Erlich HA, Fernandez-Vina M, Geraghty DE, Holdsworth R, Hurley CK, Lau M, Lee KW, Mach B, Maiers M, Mayr WR, Muller CR, Parham P, Petersdorf EW, Sasazuki T, Strominger JL, Svejgaard A, Terasaki PI, Tiercy JM, Trowsdale J (2010) Nomenclature for factors of the HLA system, 2010. Tissue Antigens 75:291–455PubMedCrossRefGoogle Scholar
- O’Connor DH, Mothe BR, Weinfurter JT, Fuenger S, Rehrauer WM, Jing P, Rudersdorf RR, Liebl ME, Krebs K, Vasquez J, Dodds E, Loffredo J, Martin S, McDermott AB, Allen TM, Wang C, Doxiadis GG, Montefiori DC, Hughes A, Burton DR, Allison DB, Wolinsky SM, Bontrop R, Picker LJ, Watkins DI (2003) Major histocompatibility complex class I alleles associated with slow simian immunodeficiency virus disease progression bind epitopes recognized by dominant acute-phase cytotoxic-T-lymphocyte responses. J Virol 77:9029–9040PubMedCrossRefGoogle Scholar
- Pinto MA, Marchevsky RS, Baptista ML, de Lima MA, Pelajo-Machado M, Vitral CL, Kubelka CF, Pissurno JW, Franca MS, Schatzmayr HG, Gaspar AM (2002) Experimental hepatitis A virus (HAV) infection in Callithrix jacchus: early detection of HAV antigen and viral fate. Exp Toxicol Pathol 53:413–420PubMedCrossRefGoogle Scholar
- Rolleke U, Flugge G, Plehm S, Schlumbohm C, Armstrong VW, Dressel R, Uchanska-Ziegler B, Ziegler A, Fuchs E, Czeh B, Walter L (2006) Differential expression of major histocompatibility complex class I molecules in the brain of a New World monkey, the common marmoset (Callithrix jacchus). J Neuroimmunol 176:39–50PubMedCrossRefGoogle Scholar
- Seehase S, Lauenstein HD, Schlumbohm C, Switalla S, Neuhaus V, Forster C, Fieguth HG, Pfennig O, Fuchs E, Kaup FJ, Bleyer M, Hohlfeld JM, Braun A, Sewald K, Knauf S (2012) LPS-induced lung inflammation in marmoset monkeys - an acute model for anti-inflammatory drug testing. PLoS One 7:e43709PubMedCrossRefGoogle Scholar
- Shiina T, Kono A, Westphal N, Suzuki S, Hosomichi K, Kita YF, Roos C, Inoko H, Walter L (2011) Comparative genome analysis of the major histocompatibility complex (MHC) class I B/C segments in primates elucidated by genomic sequencing in common marmoset (Callithrix jacchus). Immunogenetics 63:485–499PubMedCrossRefGoogle Scholar