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G G Doxiadis

Publications and source records attributed to G G Doxiadis.

9 recordsLinked to original sources
PubMed2003

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.

Certain major histocompatibility complex class I (MHC-I) alleles are associated with delayed disease progression in individuals infected with human immunodeficiency virus (HIV) and in macaques infected with simian immunodeficiency virus (SIV). However, little is known about the influence of these MHC alleles on acute-phase cellular immune responses. Here we follow 51 animals infected with SIV(mac)239 and demonstrate a dramatic association between Mamu-A*01 and -B*17 expression and slowed disease progression. We show that the dominant acute-phase cytotoxic T lymphocyte (CTL) responses in animals expressing these alleles are largely directed against two epitopes restricted by Mamu-A*01 and one epitope restricted by Mamu-B*17. One Mamu-A*01-restricted response (Tat(28-35)SL8) and the Mamu-B*17-restricted response (Nef(165-173)IW9) typically select for viral escape variants in early SIV(mac)239 infection. Interestingly, animals expressing Mamu-A*1 and -B*17 have less variation in the Tat(28-35)SL8 epitope during chronic infection than animals that express only Mamu-A*01. Our results show that MHC-I alleles that are associated with slow progression to AIDS bind epitopes recognized by dominant CTL responses during acute infection and underscore the importance of understanding CTL responses during primary HIV infection.

Alleles↗
PubMed2001

Differential evolutionary MHC class II strategies in humans and rhesus macaques: relevance for biomedical studies.

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.

Animals↗
PubMed2000

Unprecedented polymorphism of Mhc-DRB region configurations in rhesus macaques.

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.

Animals↗
PubMed2000

Major histocompatibility complex class I diversity in a West African chimpanzee population: implications for HIV research.

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.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Allelic diversity of Mhc-DRB alleles in rhesus macaques.

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.

Alleles↗
PubMed1999

Major histocompatibility complex class II polymorphisms in primates.

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.

Animals↗
PubMed1998

Characterization and distribution of Mhc-DPB1 alleles in chimpanzee and rhesus macaque populations.

Allelic diversity at the nonhuman primate Mhc-DPB1 locus was studied by determining exon 2 nucleotide sequences. This resulted in the detection of 17 chimpanzee (Pan troglodytes), 2 orangutan (Pongo pygmaeus) and 16 rhesus macaque (Macaca mulatta) alleles. These were compiled with primate Mhc-DPB1 nucleotide sequences that were published previously. Based upon the results, a sequence specific oligotyping method was developed allowing us to investigate the distribution of Mhc-DPB1 alleles in distinct chimpanzee and rhesus macaque colonies. Like found in humans, chimpanzee and rhesus macaque populations originating from different geographic backgrounds appear to be characterized by the presence of a few dominant Mhc-DPB1 alleles.

Alleles↗
PubMed1998

Characterization of the ABO blood group genes in macaques: evidence for convergent evolution.

The ABO blood group system is known to act as a major transplantation barrier in primates. Different primate species share the presence of A and B antigens. The polymorphism of the macaque ABO blood group genes was analyzed by cloning and sequencing the exon 7 region. In the case of the rhesus macaque (Macaca mulatta) and cynomolgus monkey (Macaca fascicularis) we were able to identify ABO blood group gene segments which cluster into two lineages, namely: *A/*O1 and *B. In addition allelic variation was observed. The 2 amino acid replacements at positions 266 and 268, which are thought to be crucial for A or B transferase activity, could be confirmed for both macaque species. Comparison of primate sequences shows that A and B reactivity was generated independently from each other in the hominoids and Old World monkey lineages. Hence, the primate A and B blood group genes are subject to convergent evolution.

ABO Blood-Group System↗