Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1989 Mar;86(6):1968–1972. doi: 10.1073/pnas.86.6.1968

Human major histocompatibility complex contains genes for the major heat shock protein HSP70.

C A Sargent 1, I Dunham 1, J Trowsdale 1, R D Campbell 1
PMCID: PMC286826  PMID: 2538825

Abstract

Little is known as to why a large number of human diseases are influenced by the major histocompatibility complex. In some cases, a direct involvement of the products of the polymorphic class I and class II, aas well as the less variable products of the class III, genes has been proposed. During characterization of the class III region for the presence of additional loci, we have located a duplicated locus encoding the major heat shock protein HSP70 between the complement and tumor necrosis factor genes. The HSP70 loci are 12 kilobases apart and lie 92 kilobases telomeric of the C2 gene. As HSP70 proteins have been linked with a protective role during and after cellular stress, and HSP70 analogues are often presented as antigens in bacterial and protozoal infections, this finding may have major implications with regard to the major histo-compatibility complex and associated diseases.

Full text

PDF
1968

Images in this article

1970Image
on p.1970
1970Image
on p.1970
1970Image
on p.1970
1971Image
on p.1971

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ananthan J., Goldberg A. L., Voellmy R. Abnormal proteins serve as eukaryotic stress signals and trigger the activation of heat shock genes. Science. 1986 Apr 25;232(4749):522–524. doi: 10.1126/science.3083508. [DOI] [PubMed] [Google Scholar]
  2. Batchelor J. R., McMichael A. J. Progress in understanding HLA and disease associations. Br Med Bull. 1987 Jan;43(1):156–183. doi: 10.1093/oxfordjournals.bmb.a072169. [DOI] [PubMed] [Google Scholar]
  3. Carroll M. C., Campbell R. D., Bentley D. R., Porter R. R. A molecular map of the human major histocompatibility complex class III region linking complement genes C4, C2 and factor B. Nature. 1984 Jan 19;307(5948):237–241. doi: 10.1038/307237a0. [DOI] [PubMed] [Google Scholar]
  4. Carroll M. C., Campbell R. D., Porter R. R. Mapping of steroid 21-hydroxylase genes adjacent to complement component C4 genes in HLA, the major histocompatibility complex in man. Proc Natl Acad Sci U S A. 1985 Jan;82(2):521–525. doi: 10.1073/pnas.82.2.521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Carroll M. C., Katzman P., Alicot E. M., Koller B. H., Geraghty D. E., Orr H. T., Strominger J. L., Spies T. Linkage map of the human major histocompatibility complex including the tumor necrosis factor genes. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8535–8539. doi: 10.1073/pnas.84.23.8535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chirico W. J., Waters M. G., Blobel G. 70K heat shock related proteins stimulate protein translocation into microsomes. Nature. 1988 Apr 28;332(6167):805–810. doi: 10.1038/332805a0. [DOI] [PubMed] [Google Scholar]
  7. Davis M. M., Bjorkman P. J. T-cell antigen receptor genes and T-cell recognition. Nature. 1988 Aug 4;334(6181):395–402. doi: 10.1038/334395a0. [DOI] [PubMed] [Google Scholar]
  8. Deshaies R. J., Koch B. D., Werner-Washburne M., Craig E. A., Schekman R. A subfamily of stress proteins facilitates translocation of secretory and mitochondrial precursor polypeptides. Nature. 1988 Apr 28;332(6167):800–805. doi: 10.1038/332800a0. [DOI] [PubMed] [Google Scholar]
  9. Dunham I., Sargent C. A., Trowsdale J., Campbell R. D. Molecular mapping of the human major histocompatibility complex by pulsed-field gel electrophoresis. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7237–7241. doi: 10.1073/pnas.84.20.7237. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Feinberg A. P., Vogelstein B. "A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum. Anal Biochem. 1984 Feb;137(1):266–267. doi: 10.1016/0003-2697(84)90381-6. [DOI] [PubMed] [Google Scholar]
  11. Goate A. M., Cooper D. N., Hall C., Leung T. K., Solomon E., Lim L. Localization of a human heat-shock HSP 70 gene sequence to chromosome 6 and detection of two other loci by somatic-cell hybrid and restriction fragment length polymorphism analysis. Hum Genet. 1987 Feb;75(2):123–128. doi: 10.1007/BF00591072. [DOI] [PubMed] [Google Scholar]
  12. Harrison G. S., Drabkin H. A., Kao F. T., Hartz J., Hart I. M., Chu E. H., Wu B. J., Morimoto R. I. Chromosomal location of human genes encoding major heat-shock protein HSP70. Somat Cell Mol Genet. 1987 Mar;13(2):119–130. doi: 10.1007/BF01534692. [DOI] [PubMed] [Google Scholar]
  13. Hunt C., Morimoto R. I. Conserved features of eukaryotic hsp70 genes revealed by comparison with the nucleotide sequence of human hsp70. Proc Natl Acad Sci U S A. 1985 Oct;82(19):6455–6459. doi: 10.1073/pnas.82.19.6455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Khandjian E. W., Türler H. Simian virus 40 and polyoma virus induce synthesis of heat shock proteins in permissive cells. Mol Cell Biol. 1983 Jan;3(1):1–8. doi: 10.1128/mcb.3.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kingston R. E., Baldwin A. S., Jr, Sharp P. A. Regulation of heat shock protein 70 gene expression by c-myc. Nature. 1984 Nov 15;312(5991):280–282. doi: 10.1038/312280a0. [DOI] [PubMed] [Google Scholar]
  16. Lindquist S. The heat-shock response. Annu Rev Biochem. 1986;55:1151–1191. doi: 10.1146/annurev.bi.55.070186.005443. [DOI] [PubMed] [Google Scholar]
  17. Lévi-Strauss M., Carroll M. C., Steinmetz M., Meo T. A previously undetected MHC gene with an unusual periodic structure. Science. 1988 Apr 8;240(4849):201–204. doi: 10.1126/science.3353717. [DOI] [PubMed] [Google Scholar]
  18. Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
  19. Monaco A. P., Neve R. L., Colletti-Feener C., Bertelson C. J., Kurnit D. M., Kunkel L. M. Isolation of candidate cDNAs for portions of the Duchenne muscular dystrophy gene. Nature. 1986 Oct 16;323(6089):646–650. doi: 10.1038/323646a0. [DOI] [PubMed] [Google Scholar]
  20. Pelham H. R. Hsp70 accelerates the recovery of nucleolar morphology after heat shock. EMBO J. 1984 Dec 20;3(13):3095–3100. doi: 10.1002/j.1460-2075.1984.tb02264.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Pelham H. R. Speculations on the functions of the major heat shock and glucose-regulated proteins. Cell. 1986 Sep 26;46(7):959–961. doi: 10.1016/0092-8674(86)90693-8. [DOI] [PubMed] [Google Scholar]
  22. Polla B. S. A role for heat shock proteins in inflammation? Immunol Today. 1988 May;9(5):134–137. doi: 10.1016/0167-5699(88)91199-1. [DOI] [PubMed] [Google Scholar]
  23. Res P. C., Schaar C. G., Breedveld F. C., van Eden W., van Embden J. D., Cohen I. R., de Vries R. R. Synovial fluid T cell reactivity against 65 kD heat shock protein of mycobacteria in early chronic arthritis. Lancet. 1988 Aug 27;2(8609):478–480. doi: 10.1016/s0140-6736(88)90123-7. [DOI] [PubMed] [Google Scholar]
  24. Shen C. K., Maniatis T. The organization of repetitive sequences in a cluster of rabbit beta-like globin genes. Cell. 1980 Feb;19(2):379–391. doi: 10.1016/0092-8674(80)90512-7. [DOI] [PubMed] [Google Scholar]
  25. Simon M. C., Fisch T. M., Benecke B. J., Nevins J. R., Heintz N. Definition of multiple, functionally distinct TATA elements, one of which is a target in the hsp70 promoter for E1A regulation. Cell. 1988 Mar 11;52(5):723–729. doi: 10.1016/0092-8674(88)90410-2. [DOI] [PubMed] [Google Scholar]
  26. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  27. Strachan T. Molecular genetics and polymorphism of class I HLA antigens. Br Med Bull. 1987 Jan;43(1):1–14. doi: 10.1093/oxfordjournals.bmb.a072166. [DOI] [PubMed] [Google Scholar]
  28. Tan E. M. Autoantibodies to nuclear antigens (ANA): their immunobiology and medicine. Adv Immunol. 1982;33:167–240. doi: 10.1016/s0065-2776(08)60836-6. [DOI] [PubMed] [Google Scholar]
  29. Todd J. A., Acha-Orbea H., Bell J. I., Chao N., Fronek Z., Jacob C. O., McDermott M., Sinha A. A., Timmerman L., Steinman L. A molecular basis for MHC class II--associated autoimmunity. Science. 1988 May 20;240(4855):1003–1009. doi: 10.1126/science.3368786. [DOI] [PubMed] [Google Scholar]
  30. Trowsdale J. Genetics and polymorphism: class II antigens. Br Med Bull. 1987 Jan;43(1):15–36. doi: 10.1093/oxfordjournals.bmb.a072168. [DOI] [PubMed] [Google Scholar]
  31. Welch W. J., Suhan J. P. Cellular and biochemical events in mammalian cells during and after recovery from physiological stress. J Cell Biol. 1986 Nov;103(5):2035–2052. doi: 10.1083/jcb.103.5.2035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Wu B. J., Williams G. T., Morimoto R. I. Detection of three protein binding sites in the serum-regulated promoter of the human gene encoding the 70-kDa heat shock protein. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2203–2207. doi: 10.1073/pnas.84.8.2203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Wu B., Hunt C., Morimoto R. Structure and expression of the human gene encoding major heat shock protein HSP70. Mol Cell Biol. 1985 Feb;5(2):330–341. doi: 10.1128/mcb.5.2.330. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Young D., Lathigra R., Hendrix R., Sweetser D., Young R. A. Stress proteins are immune targets in leprosy and tuberculosis. Proc Natl Acad Sci U S A. 1988 Jun;85(12):4267–4270. doi: 10.1073/pnas.85.12.4267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. van Eden W., Thole J. E., van der Zee R., Noordzij A., van Embden J. D., Hensen E. J., Cohen I. R. Cloning of the mycobacterial epitope recognized by T lymphocytes in adjuvant arthritis. Nature. 1988 Jan 14;331(6152):171–173. doi: 10.1038/331171a0. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES