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Natural variation in immune responsiveness, with special reference to immunodeficiency and promoter polymorphism in
N A Mitchison1, B Muller, R M Segal
1Department of Immunology, University College London Medical School, UK. n.mitchison@ucl.ac.uk
Abstract:
This review deals with natural selection operating on heterozygotes as a key factor controlling (a) the frequency of immunodeficiencies, and (b) promoter polymorphism in MHC class II genes. The known difference in frequency distribution of X-linked and autosomal deficiencies lend support to this possibility, and suggest that the frequency of neonatal defect may rise as old-established equlibria between entry and exit of deleterious mutations change. MHC class II gene promoters differ in their capacity to favor Th1 (or reciprocally Th2) responses, thus suggesting that promoter polymorphism is sustained by the greater flexibility in response that this confers on heterozygotes.