A primate species with limited major histocompatibility complex class I polymorphism.

Abstract

Extensive polymorphism at the major histocompatibility complex (MHC) is thought to confer immune protection on populations. A New World primate, the cottontop tamarin (Saguinis oedipus), has a high prevalence of ulcerative colitis and adenocarcinoma of the colon and dies after infection with several human viruses. Lymphocytes from all animals tested expressed one common MHC class I allelic product. Another MHC ciass I allelic product was expressed by 39 of 41 tested animals. Four other ailelic products were also expressed on the lymphocytes of these animals at a frequency of >50%. MHC class II gene products, however, were polymorphic. Restriction fragment length polymorphism analysis confirmed that there were a limited number of cotton-top tamarin MHC class I alleles, whereas the MHC class II gene loci were polymorphic. This sharing of MHC class I alleles is unprecedented in a higher primate species and may play a role in the susceptibility of this endangered species to pathogens.Major histocompatibility complex (MHC) glycoproteins play an important role in immune cell interactions. Codominant expression of class I and class II allelic products and an extraordinary degree of polymorphism of these products in a species are thought to confer a survival advantage to individuals and to the species by facilitating the ability of the immune system to interact with a variety of pathogens.Cotton-top tamarins (Saguinus oedipus) are highly susceptible to a variety of pathogenic processes. As many as 60% of captive S. oedipus spontaneously develop ulcerative colitis and 15% of these animals develop adenocarcinoma of the colon (1). S. oedipus also develops fatal lymphoproliferative syndromes after infection with Epstein-Barr virus and Herpesvirus saimiri (2, 3). Additionally, these tamarins are highly susceptible to retrovirus-induced sarcomas and fatal measle virus infections (3). Interestingly, cotton-top tamarins are usually born as dizygotic twins and an anastamosing placental circulation results in their development as naturally occurring bone-marrow-chimeric animals (4).In this study, we demonstrate that the cotton-top tamarin possesses very few allelic products at its three MHC class I loci. Its MHC, however, encodes for a diversity of class II allelic products, suggesting that its limited number of class I alleles are not due to a recent founder effect. This unprecedented limited MHC class I polymorphism in a primate species may play a role in the cotton-top tamarin's extreme susceptibility to pathogens. Celi Culture. Peripheral blood lymphocytes (PBLs) were separated from 2 to 10 ml of heparinized blood by using Dextran or Ficoll/diatrizoate gradient centrifugation. These cells were cultured at 106 cells per ml with phytohemagglutinin-P (Difco) at 1 pug/ml in RPMI 1640 medium (GIBCO) supplemented with heat-inactivated fetal bovine serum (Sterile Systems, Logan, UT) to a final concentration of 10% (vol/vol), 2 mM L-glutamine, 50 1LM 2-mercaptoethanol, 20 mM Hepes, gentamycin at 40 ,ug/ml, amphotericin B at 0...

Virus-specific cytotoxic T cell responses are associated with immunity of the cottontop tamarin to Epstein–Barr virus (EBV)

“…Both class I and class II MHC have very limited polymorphism and allelic diversity in this species [14]. The class I MHC has been shown to have three loci, but so far only 11 alleles have been discovered [15]. Furthermore, sequence data suggest that the tamarin has lost its conventional A, B and C loci and uses genes evolved from the so called atypical G and F loci in their place [16].…”

Molecular and Immunological Significance of Chimpanzee Major Histocompatibility Complex Haplotypes for Hepatitis C Virus Immune Response and Vaccination Studies

“…Collectively, these observations may indicate specific adaptations after Homo sapiens and Pan troglodytes diverged from a common ancestor five million years ago (21), and it is possible that the diversity, sequence, and function of MHC alleles have been influenced by pathogen-mediated selection. For example, it has been demonstrated that the cotton-top tamarin, a primate species characterized by very low MHC class I polymorphism, is very susceptible to fatal infections with various pathogens (52). Similarly, it has been suggested that P. troglodytes may have maintained certain MHC alleles that are not present in humans (1) but may confer a selective advantage during infections with pathogens such as HCV and HIV, because both infections are clinically less severe and more frequently cleared in chimpanzees than in humans (13).…”

Evolutionary instability of the major histocompatibility complex class I loci in New World primates

“…The cotton-top tamarin (Saguinus oedipus), a New World primate, is, in many ways, an exception to the rules of polymorphism, variability, and stability that characterize the MHC class I genes of primates (18). Cotton-top tamarins express MHC class I genes with limited polymorphism and variability.…”