Search Results - (Author, Cooperation:D. I. Watkins)

2012-10-02

Nature Publishing Group (NPG)

0028-0836

1476-4687

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

AIDS Vaccines/*immunology ; Acquired Immunodeficiency Syndrome/*virology ; Animals ; CD8-Positive T-Lymphocytes/*immunology ; Disease Models, Animal ; Epitopes, T-Lymphocyte/immunology ; Female ; HIV-1/immunology ; HLA-B27 Antigen/immunology ; Humans ; Immunodominant Epitopes/immunology ; Macaca mulatta/immunology/virology ; Male ; SAIDS Vaccines/*immunology ; Simian Acquired Immunodeficiency Syndrome/immunology/*prevention & ; control/virology ; Simian Immunodeficiency Virus/growth & development/*immunology/pathogenicity ; Viral Load ; Viremia/immunology/prevention & control ; Virus Replication/*immunology

1744-313X

Blackwell Publishing Journal Backfiles 1879-2005

Biology

Medicine

The products of the major histocompatibility complex (MHC) loci regulate an individual's immune response to pathogens. Cattle provide an important model to study the relationship between disease susceptibility and MHC haplotype since large half-sibling families are common. The definitive demonstration, however, of a firm relationship between MHC phenotype and disease susceptibility in cattle will require a precise definition of the bovine MHC allelic products. Available reagents for serological characterization of the bovine MHC gene products have not been adequate for these purposes. We have shown that existing mouse monoclonal antibodies and rabbit anti-human antisera precipitate bovine class I molecules, that these structures separate well by one-dimensional isoelectric focusing (1-DIEF), and that immunoprecipitation followed by 1-DIEF allows the detection of bovine class I MHC allelic products. Through this technique, we have identified previously undetected class I products. This approach will facilitate a detailed characterization of the bovine MHC class I gene products.

Electronic Resource

1432-1211

Key words CTL ; Escape ; SIV/HIV

Springer Online Journal Archives 1860-2000

Biology

Medicine

Electronic Resource

1432-1211

Key words MHC class I ; Pseudogene ; Evolution ; Gorilla ; Chimpanzee

Springer Online Journal Archives 1860-2000

Biology

Medicine

Electronic Resource

1432-1211

Key words MHC class I ; Cotton-top tamarin ; Influenza ; New World Primates ; Cytotoxic T lymphocytes

Springer Online Journal Archives 1860-2000

Biology

Medicine

Abstract  The products of the highly polymorphic and variable major histocompatibility complex (MHC) class I loci play a crucial role in host defenses against infectious disease. While similar alleles have been found in closely related species, sharing of a functional MHC class I allele between two species has never been reported. Here we show that an identical functional MHC class I molecule is present in two different primate species with an approximate divergence time of 0.7 million years. Lymphocytes from the red-crested tamarin (Saguinus geoffroyi) expressed an MHC class I allele (Sage-G * 01) that was identical in coding sequence to an MHC class I allele (Saoe-G * 08) found in the cotton-top tamarin (Saguinus oedipus). Furthermore, influenza virus-specific cytotoxic T lymphocytes (CTLs) generated in the cotton-top tamarin killed lymphocytes expressing the influenza virus nucleoprotein (NP) from the red-crested tamarin. Since the influenza virus NP epitope is bound by Saoe-G*08 in the cotton-top tamarin, it is likely that this molecule is functional in both species. These data provide the first evidence that functional MHC class I molecules can be maintained entirely intact in two separate species.

Electronic Resource

1432-1211

Key words Nonhuman primate ; Spondyloarthropathy ; Reactive arthritis ; Autoimmunity ; Major histocompatibility locus

Springer Online Journal Archives 1860-2000

Biology

Medicine

Abstract  The human major histocompatibility complex (MHC) class I gene, HLA-B27, is a strong risk factor for susceptibility to a group of disorders termed spondyloarthropathies. Rodents that express HLA-B27 develop spondyloarthropathies, implicating HLA-B27 in the etiology of these disorders. To determine whether an HLA-B27-like molecule was associated with spondyloarthropathies in nonhuman primates, we analyzed the MHC class I cDNAs expressed in a cohort of rhesus macaques that developed reactive arthritis after an outbreak of shigellosis. We identified several cDNAs with only limited sequence similarity to HLA-B27. Interestingly, one of these MHC molecules had a B pocket identical to that of HLA-B39. Pool sequencing of radiolabeled peptides bound by this molecule demonstrated that, like HLA-B27 and HLA-B39, it could bind peptides with arginine at the second position. However, extensive analysis of the MHC class I molecules in this cohort revealed no statistically significant association between any particular MHC class I allele and susceptibility to reactive arthritis. Furthermore, none of the rhesus MHC class I molecules bore a strong resemblance to HLA-B27, indicating that reactive arthritis can develop in this animal model in the absence of an HLA-B27-like molecule. Surprisingly, there was a statistically significant association between the rhesus macaque MHC A locus allele, Mamu-A*12, and the absence of reactive arthritis following Shigella infection.

Electronic Resource

1432-1211

Key words New world primates ; MHC ; Evolution ; Gene duplication

Springer Online Journal Archives 1860-2000

Biology

Medicine

Abstract  Lymphocytes of a New World primate, the cotton-top tamarin (Saguinus oedipus), express classical G–related major histocompatibility complex (MHC) class I molecules with unusually limited polymorphism and variability. Three G-related loci, an F locus, an E locus, and two pseudogenes (So-N1 and So-N3) have been identified by cDNA library screening and extensive PCR analysis of both cDNA and genomic DNA from the cotton-top tamarin. Furthermore, each genus of the subfamily Callitrichinae (tamarins and marmosets) appears to express its own unique set of MHC class I genes, likely due to a rapid turnover of loci. The rapid emergence of unique MHC class I genes in the Callitrichinae genera, resulting from an active process of duplication and inactivation of loci, may account for the limited diversity of the MHC class I genes in the cotton-top tamarin. To determine the nature of the entire complement of MHC class I genes in the cotton-top tamarin, we synthesized a genomic DNA library and screened it with MHC class I-specific probes. We isolated nine new MHC class I pseudogenes from this library. These newly isolated tamarin G–related MHC class I pseudogenes are not closely related to any of their functional counterparts in the tamarin, suggesting that they do not share a recent common ancestral gene with the tamarin's currently expressed MHC class I loci. In addition, these tamarin sequences display a high rate of nonsynonymous substitutions in their putative peptide binding region. This indicates that the genes from which they have derived were likely subject to positive selection and, therefore, were once functional. Our data support the notion that an extremely high rate of loci turnover is largely responsible for the limited diversity of the MHC class I genes in the cotton-top tamarin.

Electronic Resource

1432-1211

Key words MHC ; Primates ; Reproduction ; Evolution

Springer Online Journal Archives 1860-2000

Biology

Medicine

Abstract  HLA-G is a nonclassical major histocompatibility complex (MHC) class I molecule that is expressed only in the human placenta, suggesting that it plays an important role at the fetal-maternal interface. In rhesus monkeys, which have similar placentation to humans, the HLA-G orthologue is a pseudogene. However, rhesus monkeys express a novel placental MHC class I molecule, Mamu-AG, which has HLA-G-like characteristics. Phylogenetic analysis of AG alleles in two Old World primate species, the baboon and the rhesus macaque, revealed limited diversity characteristic of a nonclassical MHC class I locus. Gene trees constructed using classical and nonclassical primate MHC class I alleles demonstrated that the AG locus was most closely related to the classical A locus. Interestingly, gene tree analyses suggested that the AG alleles were most closely related to a subset of A alleles which are the products of an ancestral interlocus recombination event between the A and B loci. Calculation of the rates of synonymous and nonsynonymous substitution at the AG locus revealed that positive selection was not acting on the codons encoding the peptide binding region. In exon 4, however, the rate of nonsynonymous substitution was significantly lower than the rate of synonymous substitution, suggesting that negative selection was acting on these codons.

Electronic Resource