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Immunogenetics

Defence by diversity

Nature volume 398, pages 668–669 (1999)Cite this article

Jeffery et al.4 report that the common MHC class I type, HLA-A*02, is associated with a greater than two-fold reduction in the risk of disease induced by human T-lymphotropic virus-1 (HTLV-1). In a two-stage study, the frequency of HLA-A*02 was consistently lower in Japanese patients with disease than in infected people without disease. Each of the main HLA-A*02 subtypes present appeared protective, and the authors detected high levels of virus-specific T cells. Among the healthy carriers of HTLV-1, viral load was much less in those with HLA-A*02 — consistent with a protective role for these T cells. The HLA-A2 lineage is unusual in that it is unique to humans, and this study identifies one pathogen that may have contributed to its selection6. Carrington et al.5 report that Americans who are heterozygous for HLA-A, -B or -C antigens are protected against rapid progression to AIDS after infection with the human immunodeficiency virus-1 (HIV-1). These authors observed an increased risk of rapid disease progression with a reduction in the number of HLA-A, -B and -C types.

These studies support a pathogen-driven theory for variation (or ‘polymorphism’) of the MHC. Other mechanisms for the maintenance of polymorphism are also gaining credence. Rodents use MHC-determined odour preferences to select mates7, and preliminary behavioural studies involving sweaty T-shirts indicate that some human students may use comparable cues8. Also, HLA homozygosity (where people have only one HLA type per locus) might impair fetal survival through an unknown mechanism9.

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Figure 1: A greater diversity of human leukocyte antigens (HLAs) may protect against some infectious diseases.

References

  1. Zinkernagel, R. M. & Doherty, P. C. Nature 248, 701–702 (1974).

    Article  ADS  CAS  Google Scholar 

  2. Doherty, P. C. & Zinkernagel, R. M. Lancet 1, 1406–1409 (1975).

    Google Scholar 

  3. Doherty, P. C. & Zinkernagel, R. M. Nature 256, 50–52 (1975).

    Article  ADS  CAS  Google Scholar 

  4. Jeffery, K. J. M. et al. Proc. Natl Acad. Sci. USA 96, 3348–3353 (1999).

    Google Scholar 

  5. Carrington, M. et al. Science 283, 1748–1752 (1999).

    Google Scholar 

  6. Browning, M. & Krausa, P. Immunol. Today 17, 165–170 (1996).

    Google Scholar 

  7. Penn, D. & Potts, W. Adv. Immunol. 69, 411–436 (1998).

    Google Scholar 

  8. Wedekind, C. & Furi, S. Proc. R. Soc. Lond. B 264, 1471–1479 (1997).

    Google Scholar 

  9. Ober, C., Hyslop, T., Elias, S., Weitkamp, L. R. & Hauck, W. W. Hum. Reprod. 13, 33–38 (1998).

    Google Scholar 

  10. Hill, A. V. S. Annu. Rev. Immunol. 16, 593–617 (1998).

    Google Scholar 

  11. Thursz, M. R., Thomas, H. C., Greenwood, B. M. & Hill, A. V. Nature Genet. 17, 11–12 (1997).

    Google Scholar 

  12. Hill, A. V. S. et al. Nature 352, 595–600 (1991).

    Article  ADS  CAS  Google Scholar 

  13. Nowak, M. A. et al. Nature 375, 606–611 (1995).

    Article  ADS  CAS  Google Scholar 

  14. Apple, R. J. et al. Nature Genet. 6, 157–162 (1994).

    Google Scholar 

  15. Gilbert, S. C. et al. Science 279, 1173–1177 (1998).

    Google Scholar 

  16. Apanius, V., Penn, D., Slev, P. R., Ruff, L. R. & Potts, W. K. Crit. Rev. Immunol. 17, 179–224 (1997).

    Google Scholar 

Download references

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  1. Wellcome Trust Centre for Human Genetics and the Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK

    Adrian V. S. Hill

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  1. Adrian V. S. Hill
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Hill, A. Defence by diversity. Nature 398, 668–669 (1999). https://doi.org/10.1038/19431

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