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Biomedical subjects

D R Vining

Publications and source records attributed to D R Vining.

9 recordsLinked to original sources
PubMed1996

Importance of MHC class 1 alpha2 and alpha3 domains in the recognition of self and non-self MHC molecules.

The importance of the species of different domains of class I MHC molecules in peripheral T cell recognition and positive and negative selection was evaluated in a single system. In transgenic mice expressing AAD (containing the alpha1+alpha2 domains of HLA-A2.1 and the alpha3 domain of H-2Dd), the CTL response to influenza peptide M1(58-66) in the context of the alpha1+alpha2 domains of HLA-A2.1 was as strong as the influenza-specific H-2Db-restricted response. However, this strong response was only discernible if the target cell MHC molecule also contained a murine alpha3 domain. In contrast, the response in HLA-A2.1 transgenic mice was about 30-fold weaker, and these CTL were indifferent to the origin of the target molecule alpha3 domain. Further analysis suggested that the major impact of the murine alpha3 domain of the transgene product was to enhance positive selection of a low affinity population of AAD-restricted T cells, presumably through species-specific interaction with CD8. Surprisingly, the response to non-self human class I MHC determinants was not augmented in AAD mice, indicating that the T cells selected are narrowly focused on AAD-related structures. Further analysis indicated that the alphal+alpha2 domains as well as the alpha3 domain influenced the magnitude of the response to non-self human class I MHC determinants, and this effect was mapped to alpha2. We suggest that the alpha2 domains of murine class I molecules contain conserved structural elements that augment the avidity of T cell-class I interactions, and this is particularly important in the recognition of non-self MHC molecules.

Animals↗
PubMed1994

Association of human class I MHC alleles with the adenovirus E3/19K protein.

A panel of HLA-A and -B locus products was analyzed for their ability to associate with the adenovirus E3/19K (E19) protein in a co-immunoprecipitation assay. Three general categories of binding were identified. HLA-A2.1 and -B7 bind very well to E19. Compared with A2.1, 6- to 30-fold less E19 was associated with HLA-A3, -A1, and -Aw69; 50- to 150-fold less E19 was associated with HLA-Aw68, -B27, and -Bw58. Digestion with endoglycosidase H indicated that all levels of association resulted in inhibition of intracellular transport and processing, however, a fraction of Aw68, B27, and Bw58 escaped from intracellular retention. In contrast to the human class I molecules analyzed, transport of the murine H-2Dd molecule was not inhibited in the presence of E19. Hybrid class I molecules, in which exons encoding domains of A2.1 and H-2Dd had been exchanged, were used to define the regions of A2.1 required for E19 association. The alpha 1 and alpha 2 domains of A2.1 contain the minimum residues necessary for both stable association with E19 and subsequent inhibition of transport. A hybrid construct containing only the alpha 2 domain of A2.1 associated weakly with E19, but its post-translational processing was completely inhibited. In contrast, although a construct containing only the alpha 1 domain of A2.1 also associated weakly with E19, its intracellular transport was slowed rather than completely inhibited. Taken together, these results indicate that residues in both the alpha 1 and alpha 2 domains of A2.1 and Dd can influence stable binding of E19, with the phenotypic changes dominated by the origin of the alpha 2 domain.

Adenovirus Early Proteins↗
PubMed1992

Species specificity in the interaction of CD8 with the alpha 3 domain of MHC class I molecules.

The alpha 1 and alpha 2 domains of the class I MHC molecule constitute the putative binding site for processed peptides and the TCR, although the alpha 3 domain has been implicated as a binding site for the CD8 molecule. Species specificity in the binding of CD8 to the alpha 3 domain has been suggested as an explanation for the low xenogeneic T cell response to class I molecules, but results on this point have been conflicting and controversial. We have addressed this issue using CTL lines from HLA-A2.1 transgenic mice that specifically recognize and lyse A2.1-expressing cells infected with influenza A/PR/8 or pulsed with influenza matrix peptide M1(57-68). Species specificity was examined using transfectants that expressed hybrid molecules containing the alpha 1 and alpha 2 domains from HLA-A2.1 and the alpha 3 domain from a murine class I molecule. Lower levels of M1(57-68) peptide were required to sensitize L cell transfectants expressing a chimera that contained an H-2Dd alpha 3 domain than targets expressing the intact A2.1 molecule. However, at high doses of peptide, lysis of these two targets was similar. However, no reproducible difference in sensitization was observed using EL4 or Jurkat transfectants expressing A2.1 or A2.1 chimeric molecules that contained an H-2Kb alpha 3 domain. In all cases, however, lysis of peptide-pulsed A2.1 expressing targets was more sensitive to inhibition with anti-CD8 mAb than lysis of cells expressing these chimeric molecules. Thus, under suboptimal conditions such as low Ag density or in the presence of anti-CD8 mAb, these CTL preferentially recognize class I molecules with a murine alpha 3 domain. This suggests that there is some species specificity in the interaction of CD8 with the alpha 3 domain of the class I molecule. However, CTL recognition was inhibited by point mutations in the alpha 3 domain of HLA-A2.1 that have been shown to inhibit binding of human CD8 and recognition by human CTL, suggesting that murine CD8 interacts to some degree with human alpha 3 domains, and that similar alpha 3 domain residues may be important for murine and human CD8 binding. The relevance of these results to an understanding of low xenogeneic responses is discussed.

Animals↗
PubMed1991

Reproduction and level of intelligence.

The study was conducted in a representative Swedish rural-urban population sample of 3,064 persons. The IQ factor was determined directly by a single well established procedure. No systematic association between IQ level and the mean number of children was found.

Adult↗
PubMed1988

Recent trends in migration between core and peripheral regions in developed and advanced developing countries.

"The main finding of this article is that net internal migration to the core regions in the countries of the developed world, which subsided in the 1970s, increased in the 1980s, although not to the level of the 1960s. In some countries of northwest Europe there is a balance now in net flows between core and periphery. In the countries of the periphery of Europe and Japan net internal migration to the core regions increased slightly in the 1980s. Net migration flows to the periphery have completely reversed in Canada, and net flows out of the core regions of the United States have been significantly reduced. In eastern Europe, however, there is still moderate net migration to the core regions without any interruption as seen in western Europe, North America, and Japan. In South Korea and Taiwan rates of net migration to the core regions have been reduced from their high levels of the 1970s, but they are still quite high and show no clear sign of a break from the past."

Asia↗
PubMed1988

Research policy and review 26: where does the United States stand in the global resource scarcity debate?

"U.S. policy on world resources and population underwent a drastic shift between the 1970s and 1980s. Underlying this shift were deep and persistent divisions among social scientists and policy scientists who are students of the global resource scarcity hypothesis. This article consists of a brief review of the history of the debate between those who believe that resources are becoming increasingly scarce and those who do not. Major focuses include the ambiguities of scarcity measures, and economic literature such as The Limits to Growth, Global 2000, the critique of Julian Simon, and The Resourceful Earth."

Americas↗
PubMed1986

Population redistribution towards core areas of less developed countries, 1950-1980.

"This paper presents estimates of the rate of population redistribution to the core areas of 44 developing countries over the period 1950-80. Particular attention is given to the period 1970-80, a time during which the core areas of developed countries experienced substantial declines in their rates of net inmigration. The principal finding is that the core areas of most developing countries are still experiencing high and, in a number of cases, increasing rates of net inmigration." The author contends that "this finding confirms the developmental model of spatial concentration and dispersal and should lay to rest other explanations of deconcentration, including arguments that focus on diseconomies of absolute size in the core area or on fluctuations in the aggregate economy." The difference between the population growth rates of entire nations and of core areas is used as a measure of interregional migration. Data for the 44 countries and information on the data sources are included in appendixes.

Demography↗