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Example sentences for: zinkernagel
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As noted by Doherty and Zinkernagel [ 4 ] , simple dominance for resistance to each of several diseases can create allele-specific overdominance for total fitness, if different alleles confer resistance to different diseases [ 10 31 ] . For these reasons, our results, while relevant to the longstanding debate over the relative importance of various kinds of balancing selection in maintaining MHC diversity [ 32 ] , raise doubts about only one of several lines of evidence for the overdominance hypothesis.
A second, distinct but compatible hypothesis was suggested by Doherty and Zinkernagel soon after their discovery of MHC restriction: since each MHC allele provides an infected individual with the ability to present a particular set of antigens, individuals who are heterozygous (say, genotype XY) at a particular MHC locus may mount a more vigorous immune response to a given infection, resulting in a better outcome, than individuals who are homozygous for either of the corresponding alleles (XX or YY) [ 4 ] .
The role of genetics in modulating the immune response to infectious diseases is a topic of longstanding interest among epidemiologists, clinicians, population geneticists, and immunologists [ 1 2 ] . Zinkernagel and Doherty's Nobel Prize-winning discovery that cellular immunity to viral infections was "restricted" by the highly variable proteins of the Major Histocompatibility Complex (MHC) brought the field of immunogenetics into sharper focus [ 3 ] . Their demonstration that T lymphocytes recognize virus antigens displayed on a host cell "in the context of" MHC proteins immediately suggested the idea that genetic differences at the loci encoding the MHC might modulate the intensity and effectiveness of host response to infection.
Doherty and Zinkernagel [ 20 ] demonstrated using congenic mice that MHC homozygotes had more vigorous immune responses to lymphocytic choriomeningitis virus (LCMV) than the corresponding homozygotes, but since the pathology of the infection they used is due to the immune response, the enhanced immune response actually resulted in reduced survival.
Although population heterozygote advantage and allele-specific overdominance are different [ 10 ] , reports of population heterozygote advantage have frequently been interpreted as confirmations of the Doherty-Zinkernagel hypothesis of allele-specific overdominance.
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