R E Bontrop

Publications (102)421 Total impact

• Article: TRIM5 allelic polymorphism in macaque species/populations of different geographic origins: its impact on SIV vaccine studies.

  N G de Groot, C M C Heijmans, G Koopman, E J Verschoor, W M Bogers, R E Bontrop
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  ABSTRACT: Tripartite motif 5α (TRIM5α) is a potent antiretroviral immune factor present in the cytoplasm of cells of most tissue types. The rhesus macaque TRIM5 gene has been shown to display polymorphism, with different variants being divided into three groups (TRIM5(TFP), TRIM5(Q), and TRIM5(CypA)), which may have divergent retroviral effects on infection. Along with rhesus macaques, cynomolgus macaques are also used in simian immunodeficiency virus (SIV) infection studies. As a consequence, TRIM5 genotyping of these animals will contribute to interpreting the outcome of such studies. The present communication covers Burmese, Chinese, and a large cohort of Indian-origin rhesus macaques, and describes the first large cohort study on TRIM5 polymorphism in outbred cynomolgus macaques. We demonstrate the presence of the TRIM5(TFP) group in cynomolgus macaques. In addition, we have re-evaluated historical samples of rhesus macaques challenged with SIV(mac251), a virus that has been reported to be partially suppressed by particular rhesus macaque TRIM5 variants.
  Tissue Antigens 10/2011; 78(4):256-62. · 2.59 Impact Factor
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  Available from: Nel Otting

  Article: Novel major histocompatibility complex class I alleles extracted from two rhesus macaque populations.

  N Otting, A Mörner, R E Bontrop
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  ABSTRACT: We report here the novel Mamu-A and -B alleles that were detected in two groups of rhesus monkeys.
  Tissue Antigens 10/2010; 77(1):79-80. · 2.59 Impact Factor
• Article: High resolution definition of HLA-DRB haplotypes by a simplified microsatellite typing technique.

  G G M Doxiadis, N de Groot, E-M Dauber, P H van Eede, I Fae, R Faner, G Fischer, Z Grubic, N M Lardy, W Mayr, E Palou, W Swelsen, K Stingl, I I N Doxiadis, R E Bontrop
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  ABSTRACT: In humans, the region configurations DR1, DR8, DR51, DR52 and DR53 are known to display copy number as well as allelic variation, rendering high resolution typing of HLA-DRB haplotypes cumbersome. Advantage was taken of microsatellite D6S2878, present in all DRB genes/pseudogenes with an intact exon 2-intron 2 segment. This DRB-STR is highly polymorphic in composition and length. Recently, it was proven that all exon 2 sequences could be linked to a certain DRB-STR that segregates with the respective DRB allele. Because haplotypes show differential copy numbers and compositions of exon 2-positive DRB genes/pseudogenes, unique DRB-STR patterns could be described that appear to be specific for a particular DRB haplotype. The aim of this workshop project was to approve and to qualify this simple typing protocol in a larger panel covering different European populations. All participants succeeded in correctly defining the DRB-STR amplicons varying from 135 to 222 base pair (bp) lengths. The panel of 101 samples covered 50 DRB alleles distributed over 37 different haplotypes as defined by exon 2 sequence-based typing. These haplotypes could be refined into 105 haplotypes by DRB-STR typing. Thus, discrimination of exon 2-identical DRB alleles was feasible, as well as the exact description of three different crossing-over events that resulted in the generation of hybrid DR region configurations. This typing procedure appears to be a quick and highly robust technique that can easily be performed by different laboratories, even without experience in microsatellite typing; thus, it is suitable for a variety of researchers in diverse research areas.
  Tissue Antigens 09/2009; 74(6):486-93. · 2.59 Impact Factor
• Article: Polymorphisms within the HLA‐DR4 haplotypes

  R. E. Bontrop, G. M. Schreuder, E. M. A. Mikulski, R. T. Miltenburg, M. J. Giphart
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  ABSTRACT: Polymorphisms among HLA class II molecules expressed by cells with different HLA-DR4 haplotypes were analysed biochemically (isoelectrofocussing and 2D gels), cellularly (HLA-Dw) and serologically (monoclonal antibodies). The results confirm the correlation which exists between HLA-D specificity and DR beta chain isoelectric point polymorphism.Furthermore, a biochemical polymorphism was observed among DQw3 molecules. No correlation was found with HLA-Dw types. On the other hand a correlation was found between DQ-polymorphism and TA10 and 2B3 specificities defined by monoclonal antibodies. The comparison of different methods defining polymorphisms of HLA class II molecules will be discussed.
  Tissue Antigens 12/2008; 27(1):22 - 31. · 2.59 Impact Factor
• Article: MIC gene polymorphism and haplotype diversity in rhesus macaques.

  G G M Doxiadis, C M Heijmans, N Otting, R E Bontrop
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  ABSTRACT: Rhesus macaques (Macaca mulatta) mainly originating from India were analysed for their major histocompatibility complex class I-related (MIC) gene repertoire. Thus far, three distinct genes, designated MIC1, MIC2 and MIC3, have been identified in the rhesus macaque. In addition, an MICD pseudogene has been described mapping apart from the other loci in a telomeric direction. Genomic comparisons and the presence of a characteristic microsatellite in exon 5 suggest that the MIC1 gene is the equivalent of the human MICA gene. Hence, the MIC2 gene, lacking the microsatellite - as do humans -, is considered to be the equivalent of human MICB. The MIC3 gene, a hybrid of MICA and MICB, seems to be generated by a crossing-over event with one breakpoint in intron 3 and accordingly is named MICA/B. Apart from their human counterparts, MICA, MICB and MICA/B cluster in separate branches in the phylogenetic tree, confirming the hybrid character of the MICA/B gene. Population analyses have shown that the various genes display polymorphism, and six MICA, five MICB and three MICA/B alleles have been identified. In the panel of homozygous typing cells, two distinct haplotype configurations have been defined by segregation analyses. Each haplotype comprises an MICB gene in conjunction with either an MICA or an MICA/B gene. Furthermore, the presence of a polymorphic microsatellite in the MICA and MICA/B alleles facilitates speedy and accurate haplotyping.
  Tissue Antigens 04/2007; 69(3):212-9. · 2.59 Impact Factor
• Article: The diallelic locus encoding the minor histocompatibility antigen HA-1 is evolutionarily conserved.

  B Wieles, J Pool, M Wilke, M Weber, H-J Kolb, R E Bontrop, E Goulmy
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  ABSTRACT: The polymorphic minor histocompatibility antigen HA-1 induces powerful T-cell alloreactivities with important consequences for graft-vs-tumor activity and development of graft-vs-host disease in patients after human leukocyte antigen-matched stem-cell transplantation (SCT). In view of possible translational animal studies, we analyzed the evolutionary conservation of the diallelic HA-1 locus in four mammalian species. Our results show that rodents do not encode the HA-1(H) allele, neither show polymorphism in this position on the HA-1 gene. Contrariwise, the HA-1(H) allele is present in non-human primate species and dogs. Interestingly, both the HA-1(H) T-cell epitope and its non-immunogenic counterpart HA-1(R) are present in the latter species. Thus, the HA-1 allelic polymorphism is conserved in evolution in primates and dogs.
  Tissue Antigens 08/2006; 68(1):62-5. · 2.59 Impact Factor
• Article: Allelic polymorphism in introns 1 and 2 of the HLA-DQA1 gene.

  C E M Voorter, N G de Groot, C M H Meertens, R E Bontrop, E M van den Berg-Loonen
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  ABSTRACT: Human leukocyte antigen (HLA) class II antigens are highly polymorphic membrane glycoproteins, encoded by the A and B genes of DR, DQ, and DP. The polymorphism is mainly located in exon 2, with the exception of DQA1. Of the 27 DQA1 alleles presently known, 18 cannot be identified on the basis of exon 2 alone, but need additional information from the other exons. DQA1 has been reported to be the most ancient class II gene. For evolutionary comparison and to assess the degree of polymorphism outside the exons, the sequences of introns 1 and 2 were determined from 30 different cell lines, encompassing 15 different DQA1 alleles. The sequences revealed major nucleotide differences between the different lineages, whereas within each lineage few differences were present. Phylogenetic analysis of intron and exon sequences confirmed this lineage specificity. Altogether, the present data indicate that the HLA-DQA1 lineages represent ancient entities. The observed variation of the introns in alleles with identical exon sequences implicates conservative selection of the exons within a given lineage. Intron sequences may provide the means to set up an accurate typing system.
  Tissue Antigens 02/2005; 65(1):56-66. · 2.59 Impact Factor
• Article: Allelic polymorphism in introns 1 and 2 of the HLA‐DQA1 gene

  C.E.M. Voorter, N.G. De Groot, C.M.H. Meertens, R.E. Bontrop, E.M. Van Den Berg-Loonen
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  ABSTRACT:   Human leukocyte antigen (HLA) class II antigens are highly polymorphic membrane glycoproteins, encoded by the A and B genes of DR, DQ, and DP. The polymorphism is mainly located in exon 2, with the exception of DQA1. Of the 27 DQA1 alleles presently known, 18 cannot be identified on the basis of exon 2 alone, but need additional information from the other exons. DQA1 has been reported to be the most ancient class II gene. For evolutionary comparison and to assess the degree of polymorphism outside the exons, the sequences of introns 1 and 2 were determined from 30 different cell lines, encompassing 15 different DQA1 alleles. The sequences revealed major nucleotide differences between the different lineages, whereas within each lineage few differences were present. Phylogenetic analysis of intron and exon sequences confirmed this lineage specificity. Altogether, the present data indicate that the HLA-DQA1 lineages represent ancient entities. The observed variation of the introns in alleles with identical exon sequences implicates conservative selection of the exons within a given lineage. Intron sequences may provide the means to set up an accurate typing system.
  Tissue Antigens 12/2004; 65(1):56 - 66. · 2.59 Impact Factor
• Article: Non-human primate models of multiple sclerosis.

  H P Brok, J Bauer, M Jonker, E Blezer, S Amor, R E Bontrop, J D Laman, B A 't Hart
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  ABSTRACT: The phylogenetic proximity between non-human primate species and humans is reflected by a high degree of immunological similarity. Non-human primates therefore provide important experimental models for disorders in the human population that are caused by the immune system, such as autoimmune diseases. In this paper we describe non-human primate models of multiple sclerosis, a chronic inflammatory and demyelinating disease of the human central nervous system. While reviewing data from the literature and our own research we will discuss the unique role of such models in the research of basic disease mechanisms and the development of new therapies.
  Immunological Reviews 11/2001; 183:173-85. · 11.15 Impact Factor
• Article: Differential evolutionary MHC class II strategies in humans and rhesus macaques: relevance for biomedical studies.

  G G Doxiadis, N Otting, N G de Groot, R E Bontrop
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  ABSTRACT: The rhesus macaque is an important preclinical model in transplantation research and in investigations of chronic and infectious diseases that need a well-characterised major histocompatibility complex (MHC-Mamu). In a large population of pedigreed rhesus macaques, 70 Mamu-DRB, 18 -DQA1, 24 -DQB1, and 14 -DPB1 alleles were detected. In humans, five HLA-DRB region configurations are present, displaying diversity with regard to number and combinations of loci. The HLA-DRB1 gene of each of these configurations is highly polymorphic. For rhesus monkeys, at least 31 Mamu-DRB region configurations have been determined. In contrast to humans, most Mamu-DRB region configurations display no or only limited allelic polymorphism. Segregation analyses revealed 28 Mamu-DQA1/DQB1 pairs, each pair linked to a limited number of Mamu-DRB region configurations and vice versa. In comparison with humans, the degree of freedom of recombination between Mamu-DQA1 and -DQB1 is extremely low and equivalents of HLA-DQA2/DQB2 are absent. The Mamu-DPA1 gene is invariant and -DPB1 manifests only moderate allelic variation, whereas the HLA-DPA1 gene is oligomorphic and HLA-DPB1 highly polymorphic. Thus, both species used different evolutionary strategies to create polymorphism and diversity at the MHC class II loci in order to cope with pathogens.
  Immunological Reviews 11/2001; 183:76-85. · 11.15 Impact Factor
• Article: Prophylactic and therapeutic effects of a humanized monoclonal antibody against the IL-2 receptor (DACLIZUMAB) on collagen-induced arthritis (CIA) in rhesus monkeys.

  H P Brok, J M Tekoppele, J Hakimi, J A Kerwin, E M Nijenhuis, C W De Groot, R E Bontrop, B A 't Hart
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  ABSTRACT: CIA in the rhesus monkey is an autoimmune-based polyarthritis with inflammation and erosion of synovial joints that shares various features with human rheumatoid arthritis (RA). The close phylogenetic relationship between man and rhesus monkey makes the model very suitable for preclinical safety and efficacy testing of new therapeutics with exclusive reactivity in primates. In this study we have investigated the prophylactic and therapeutic effects of a humanized monoclonal antibody (Daclizumab) against the alpha-chain of the IL-2 receptor (CD25). When Daclizumab treatment was started well after immunization but before the expected onset of CIA a significant reduction of joint-inflammation and joint-erosion was observed. A therapeutic treatment, initiated as soon as the first clinical signs of CIA were observed, proved also effective since joint-degradation was abrogated. The results of this study indicate that Daclizumab has clinical potential for the treatment of RA during periods of active inflammation and suppression of the destruction of the joint tissues.
  Clinical & Experimental Immunology 05/2001; 124(1):134-41. · 3.36 Impact Factor
• Article: Myelin/oligodendrocyte glycoprotein-induced autoimmune encephalomyelitis in common marmosets: the encephalitogenic T cell epitope pMOG24-36 is presented by a monomorphic MHC class II molecule.

  H P Brok, A Uccelli, N Kerlero De Rosbo, R E Bontrop, L Roccatagliata, N G de Groot, E Capello, J D Laman, K Nicolay, G L Mancardi, A Ben-Nun, B A Hart
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  ABSTRACT: Immunization of common marmosets (Callithrix jacchus) with a single dose of human myelin in CFA, without administration of Bordetella pertussis, induces a form of autoimmune encephalomyelitis (EAE) resembling in its clinical and pathological expression multiple sclerosis in humans. The EAE incidence in our outbred marmoset colony is 100%. This study was undertaken to assess the genetic and immunological basis of the high EAE susceptibility. To this end, we determined the separate contributions of immune reactions to myelin/oligodendrocyte glycoprotein (MOG) and myelin basic protein to the EAE induction. Essentially all pathological features of myelin-induced EAE were also found in animals immunized with MOG in CFA, whereas in animals immunized with myelin basic protein in CFA clinical and pathological signs of EAE were lacking. The epitope recognition by anti-MOG Abs and T cells were assessed. Evidence is provided that the initiation of EAE is based on T and B cell activation by the encephalitogenic phMOG14-36 peptide in the context of monomorphic Caja-DRB*W1201 molecules.
  The Journal of Immunology 08/2000; 165(2):1093-101. · 5.79 Impact Factor
• Article: Definition of five new simian immunodeficiency virus cytotoxic T-lymphocyte epitopes and their restricting major histocompatibility complex class I molecules: evidence for an influence on disease progression.

  D T Evans, P Jing, T M Allen, D H O'Connor, H Horton, J E Venham, M Piekarczyk, J Dzuris, M Dykhuzen, J Mitchen, R A Rudersdorf, C D Pauza, A Sette, R E Bontrop, R DeMars, D I Watkins
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  ABSTRACT: Simian immunodeficiency virus (SIV) infection of the rhesus macaque is currently the best animal model for AIDS vaccine development. One limitation of this model, however, has been the small number of cytotoxic T-lymphocyte (CTL) epitopes and restricting major histocompatibility complex (MHC) class I molecules available for investigating virus-specific CTL responses. To identify new MHC class I-restricted CTL epitopes, we infected five members of a family of MHC-defined rhesus macaques intravenously with SIV. Five new CTL epitopes bound by four different MHC class I molecules were defined. These included two Env epitopes bound by Mamu-A*11 and -B*03 and three Nef epitopes bound by Mamu-B*03, -B*04, and -B*17. All four restricting MHC class I molecules were encoded on only two haplotypes (b or c). Interestingly, resistance to disease progression within this family appeared to be associated with the inheritance of one or both of these MHC class I haplotypes. Two individuals that inherited haplotypes b and c separately survived for 299 and 511 days, respectively, while another individual that inherited both haplotypes survived for 889 days. In contrast, two MHC class I-identical individuals that did not inherit either haplotype rapidly progressed to disease (survived <80 days). Since all five offspring were identical at their Mamu-DRB loci, MHC class II differences are unlikely to account for their patterns of disease progression. These results double the number of SIV CTL epitopes defined in rhesus macaques and provide evidence that allelic differences at the MHC class I loci may influence rates of disease progression among AIDS virus-infected individuals.
  Journal of Virology 08/2000; 74(16):7400-10. · 5.40 Impact Factor
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  Available from: Nel Otting

  Article: Allelic diversity of Mhc-DRB alleles in rhesus macaques.

  N Otting, N G de Groot, M C Noort, G G Doxiadis, R E Bontrop
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  ABSTRACT: The Biomedical Primate Research Centre (BPRC) rhesus macaque colony was started with a large number of wild-caught animals originating mainly from the Indian subcontinent. The contemporary self-sustaining colony comprises approximately 800 individuals. We screened a large section of the colony for Mamu-DRB polymorphisms by applying the denaturing gradient gel electrophoresis (DGGE) technique. Based on disparate DGGE profiles, animals were selected for nucleotide sequence analysis. This approach allowed the detection of 25 unreported Mamu-DRB alleles, bringing to 126 the total number of alleles documented in the literature. This communication demonstrates that rhesus macaques, like humans, display extensive allelic polymorphism at the DRB region. Phylogenetic analyses illustrate that humans and rhesus macaques share several Mhc-DRB loci and lineages. Identical exon 2 sequences, however, which are shared between humans and rhesus macaques, were not observed. This indicates that most primate Mhc-DRB alleles are of post-speciation origin.
  Tissue Antigens 08/2000; 56(1):58-68. · 2.59 Impact Factor
• Article: Major histocompatibility complex class I diversity in a West African chimpanzee population: implications for HIV research.

  N G de Groot, N Otting, R Argüello, D I Watkins, G G Doxiadis, J A Madrigal, R E Bontrop
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  ABSTRACT: Human immunodeficiency virus (HIV) poses a major threat to humankind. And though, like humans, chimpanzees are susceptible to HIV infection, they are considered to be resistant to the development of the acquired immune deficiency syndrome (AIDS). Little is known about major histocompatibility complex (MHC) class I diversity in chimpanzee populations and, moreover, whether qualitative aspects of Patr class I molecules may control resistance to AIDS. To address these questions, we assayed MHC class I diversity in a West African chimpanzee population and in some animals from other subspecies of chimpanzee. Application of different techniques allowed the detection of 17 full-length Patr-A, 19 Patr-B, and 10 Patr-C alleles. All Patr-A alleles cluster only into the HLA-A1/A3/A11 family, which supports the idea that chimpanzees have experienced a reduction in their repertoire of A locus alleles. The Patr-B alleles do not cluster in the same lineages as their human equivalents, due to frequent exchange of polymorphic sequence motifs. Furthermore, polymorphic motifs may have been exchanged between Patr-A and Patr-B loci, resulting in convergence. With regard to evolutionary stability, the Patr-C locus is more similar to the Patr-A locus than it is to the Patr-B locus. Despite the relatively low number of animals analyzed, humans and chimpanzees were ascertained as sharing similar degrees of diversity at the contact residues constituting the B and F pockets in the peptide-binding side of MHC class I molecules. Our results indicate that within a small sample of a West African chimpanzee population, a high degree of Patr class I diversity is encountered. This is in agreement with the fact that chimpanzees display more mitochondrial DNA variation than humans. In addition, population analyses demonstrated that particular Patr-B molecules, with the capacity to bind conserved HIV-1 epitopes, are characterized by high gene frequencies. These findings have important implications for evaluating immune responses in HIV vaccine studies and, more importantly, may help in understanding the relative resistance of chimpanzees to AIDS.
  Immunogenetics 06/2000; 51(6):398-409. · 2.93 Impact Factor
• Article: Unprecedented polymorphism of Mhc-DRB region configurations in rhesus macaques.

  G G Doxiadis, N Otting, N G de Groot, R Noort, R E Bontrop
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  ABSTRACT: The rhesus macaque is an important model in preclinical transplantation research and for the study of chronic and infectious diseases, and so extensive knowledge of its MHC (MhcMamu) is needed. Nucleotide sequencing of exon 2 allowed the detection of 68 Mamu-DRB alleles. Although most alleles belong to loci/lineages that have human equivalents, identical Mhc-DRB alleles are not shared between humans and rhesus macaques. The number of -DRB genes present per haplotype can vary from two to seven in the rhesus macaque, whereas it ranges from one to four in humans. Within a panel of 210 rhesus macaques, 24 Mamu-DRB region configurations can be distinguished differing in the number and composition of loci. None of the Mamu-DRB region configurations has been described for any other species, and only one of them displays major allelic variation giving rise to a total of 33 Mamu-DRB haplotypes. In the human population, only five HLA-DRB region configurations were defined, which in contrast to the rhesus macaque exhibit extensive allelic polymorphism. In comparison with humans, the unprecedented polymorphism of the Mamu-DRB region configurations may reflect an alternative strategy of this primate species to cope with pathogens. Because of the Mamu-DRB diversity, nonhuman primate colonies used for immunological research should be thoroughly typed to facilitate proper interpretation of results. This approach will minimize as well the number of animals necessary to conduct experiments.
  The Journal of Immunology 04/2000; 164(6):3193-9. · 5.79 Impact Factor
• Article: Mamu-I: a novel primate MHC class I B-related locus with unusually low variability.

  J A Urvater, N Otting, J H Loehrke, R Rudersdorf, I I Slukvin, M S Piekarczyk, T G Golos, A L Hughes, R E Bontrop, D I Watkins
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  ABSTRACT: The rhesus macaque is an important animal model for several human diseases and organ transplantation. Therefore, definition of the MHC of this species is crucial to the development of these models. Unfortunately, unlike humans, lymphocytes from a single rhesus macaque express up to 12 different MHC class I cDNAs. From which locus these various alleles are derived is unclear. In our attempts to define the MHC class I loci of the rhesus macaque, we have identified an unusual MHC class I locus, Mamu-I. We isolated 26 I locus alleles from three different macaque species but not from three other Cercopithecine genera, suggesting that the I locus is the result of a recent duplication of the B locus occurring after the divergence of macaques from the ancestor of the other extant Cercopithecine genera. Mamu-I mRNA transcripts were detected in all tissues examined and Mamu-I protein was produced in rhesus B lymphoblastoid cell lines. Furthermore, Mamu-I protein was detected by flow cytometry on the surface of human 721.221 cells transfected with Mamu-I. In contrast to the polymorphism present at this locus, there is unusually low sequence variability, with the mean number of nucleotide differences between alleles being only 3.6 nt. Therefore, Mamu-I is less variable than any other polymorphic MHC class I locus described to date. Additionally, no evidence for positive selection on the peptide binding region was observed. Together, these results suggest that Mamu-I is an MHC class I locus in primates that has features of both classical and nonclassical loci.
  The Journal of Immunology 03/2000; 164(3):1386-98. · 5.79 Impact Factor
• Article: The major histocompatibility complex class II region of the chimpanzee: towards a molecular map.

  N G de Groot, R E Bontrop
  Immunogenetics 12/1999; 50(3-4):160-7. · 2.93 Impact Factor
• Source

  Available from: wisc.edu

  Article: Virus-specific cytotoxic T-lymphocyte responses select for amino-acid variation in simian immunodeficiency virus Env and Nef.

  D T Evans, D H O'Connor, P Jing, J L Dzuris, J Sidney, J da Silva, T M Allen, H Horton, J E Venham, R A Rudersdorf, T Vogel, C D Pauza, R E Bontrop, R DeMars, A Sette, A L Hughes, D I Watkins
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  ABSTRACT: Cytotoxic T-lymphocyte (CTL) responses to human immunodeficiency virus arise early after infection, but ultimately fail to prevent progression to AIDS. Human immunodeficiency virus may evade the CTL response by accumulating amino-acid replacements within CTL epitopes. We studied 10 CTL epitopes during the course of simian immunodeficiency virus disease progression in three related macaques. All 10 of these CTL epitopes accumulated amino-acid replacements and showed evidence of positive selection by the time the macaques died. Many of the amino-acid replacements in these epitopes reduced or eliminated major histocompatibility complex class I binding and/or CTL recognition. These findings strongly support the CTL 'escape' hypothesis.
  Nature Medicine 12/1999; 5(11):1270-6. · 22.46 Impact Factor
• Article: Major histocompatibility complex class II polymorphisms in primates.

  R E Bontrop, N Otting, N G de Groot, G G Doxiadis
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  ABSTRACT: In the past decade, the major histocompatibility complex (MHC) class II region of several primate species has been investigated extensively. Here we will discuss the similarities and differences found in the MHC class II repertoires of primate species including humans, chimpanzees, rhesus macaques, cotton-top tamarins and common marmosets. Such types of comparisons shed light on the evolutionary stability of MHC class II alleles, lineages and loci as well as on the evolutionary origin and biological significance of haplotype configurations.
  Immunological Reviews 03/1999; 167:339-50. · 11.15 Impact Factor