Skip to main content
NCBI home page
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1985 Jun;5(6):1295–1300. doi: 10.1128/mcb.5.6.1295

Stable transfer and restricted expression of a cloned class I gene encoding a secreted transplantation-like antigen.

Y Barra, K Tanaka, K J Isselbacher, G Khoury, G Jay
PMCID: PMC366857  PMID: 4033655

Abstract

The identification of a unique major histocompatibility complex class I gene, designated Q10, which encodes a secreted rather than a cell surface antigen has led to questions regarding its potential role in regulating immunological functions. Since the Q10 gene is specifically activated only in the liver, we sought to define the molecular mechanisms which control its expression in a tissue-specific fashion. Results obtained by transfection of the cloned Q10 gene, either in the absence or presence of a heterologous transcriptional enhancer, into a variety of cell types of different tissue derivations are consistent with the Q10 gene being regulated at two levels. The first is by a cis-dependent mechanism which appears to involve site-specific DNA methylation. The second is by a trans-acting mechanism which would include the possibility of an enhancer binding factor. The ability to efficiently express the Q10 gene in certain transfected cell lines offers an opportunity to obtain this secreted class I antigen in quantities sufficient for functional studies; this should also make it possible to define regulatory sequences which may be responsible for the tissue-specific expression of Q10.

Full text

PDF
1295

Images in this article

1296Image
on p.1296
1297Image
on p.1297
1298Image
on p.1298

Selected References

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

  1. Calne R. Y., Sells R. A., Pena J. R., Davis D. R., Millard P. R., Herbertson B. M., Binns R. M., Davies D. A. Induction of immunological tolerance by porcine liver allografts. Nature. 1969 Aug 2;223(5205):472–476. doi: 10.1038/223472a0. [DOI] [PubMed] [Google Scholar]
  2. Cosman D., Khoury G., Jay G. Three classes of mouse H-2 messenger RNA distinguished by analysis of cDNA clones. Nature. 1982 Jan 7;295(5844):73–76. doi: 10.1038/295073a0. [DOI] [PubMed] [Google Scholar]
  3. Cosman D., Kress M., Khoury G., Jay G. Tissue-specific expression of an unusual H-2 (class I)-related gene. Proc Natl Acad Sci U S A. 1982 Aug;79(16):4947–4951. doi: 10.1073/pnas.79.16.4947. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Evans G. A., Margulies D. H., Camerini-Otero R. D., Ozato K., Seidman J. G. Structure and expression of a mouse major histocompatibility antigen gene, H-2Ld. Proc Natl Acad Sci U S A. 1982 Mar;79(6):1994–1998. doi: 10.1073/pnas.79.6.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Feldmann G. Morphologic aspects of hepatic synthesis and secretion of plasma proteins. Prog Liver Dis. 1979;6:23–41. [PubMed] [Google Scholar]
  6. Gillies S. D., Folsom V., Tonegawa S. Cell type-specific enhancer element associated with a mouse MHC gene, E beta. Nature. 1984 Aug 16;310(5978):594–597. doi: 10.1038/310594a0. [DOI] [PubMed] [Google Scholar]
  7. Gorman C. M., Merlino G. T., Willingham M. C., Pastan I., Howard B. H. The Rous sarcoma virus long terminal repeat is a strong promoter when introduced into a variety of eukaryotic cells by DNA-mediated transfection. Proc Natl Acad Sci U S A. 1982 Nov;79(22):6777–6781. doi: 10.1073/pnas.79.22.6777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
  9. Hankinson O. Single-step selection of clones of a mouse hepatoma line deficient in aryl hydrocarbon hydroxylase. Proc Natl Acad Sci U S A. 1979 Jan;76(1):373–376. doi: 10.1073/pnas.76.1.373. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Howley P. M., Sarver N., Law M. F. Eukaryotic cloning vectors derived from bovine papillomavirus DNA. Methods Enzymol. 1983;101:387–402. doi: 10.1016/0076-6879(83)01029-0. [DOI] [PubMed] [Google Scholar]
  11. Kamada N., Davies H. S., Roser B. Reversal of transplantation immunity by liver grafting. Nature. 1981 Aug 27;292(5826):840–842. doi: 10.1038/292840a0. [DOI] [PubMed] [Google Scholar]
  12. Klein J. The major histocompatibility complex of the mouse. Science. 1979 Feb 9;203(4380):516–521. doi: 10.1126/science.104386. [DOI] [PubMed] [Google Scholar]
  13. Kress M., Cosman D., Khoury G., Jay G. Secretion of a transplantation-related antigen. Cell. 1983 Aug;34(1):189–196. doi: 10.1016/0092-8674(83)90149-6. [DOI] [PubMed] [Google Scholar]
  14. Maloy W. L., Coligan J. E., Barra Y., Jay G. Detection of a secreted form of the murine H-2 class I antigen with an antibody against its predicted carboxyl terminus. Proc Natl Acad Sci U S A. 1984 Feb;81(4):1216–1220. doi: 10.1073/pnas.81.4.1216. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mellor A. L., Weiss E. H., Kress M., Jay G., Flavell R. A. A nonpolymorphic class I gene in the murine major histocompatibility complex. Cell. 1984 Jan;36(1):139–144. doi: 10.1016/0092-8674(84)90082-5. [DOI] [PubMed] [Google Scholar]
  16. Mellor A. L., Weiss E. H., Ramachandran K., Flavell R. A. A potential donor gene for the bm1 gene conversion event in the C57BL mouse. Nature. 1983 Dec 22;306(5945):792–795. doi: 10.1038/306792a0. [DOI] [PubMed] [Google Scholar]
  17. Morrison B., Kress M., Khoury G., Jay G. Simian virus 40 tumor antigen: isolation of the origin-specific DNA-binding domain. J Virol. 1983 Jul;47(1):106–114. doi: 10.1128/jvi.47.1.106-114.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Pease L. R., Schulze D. H., Pfaffenbach G. M., Nathenson S. G. Spontaneous H-2 mutants provide evidence that a copy mechanism analogous to gene conversion generates polymorphism in the major histocompatibility complex. Proc Natl Acad Sci U S A. 1983 Jan;80(1):242–246. doi: 10.1073/pnas.80.1.242. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Rothstein S. J., Reznikoff W. S. The functional differences in the inverted repeats of Tn5 are caused by a single base pair nonhomology. Cell. 1981 Jan;23(1):191–199. doi: 10.1016/0092-8674(81)90284-1. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Stafford J., Queen C. Cell-type specific expression of a transfected immunoglobulin gene. Nature. 1983 Nov 3;306(5938):77–79. doi: 10.1038/306077a0. [DOI] [PubMed] [Google Scholar]
  22. Tanaka K., Appella E., Jay G. Developmental activation of the H-2K gene is correlated with an increase in DNA methylation. Cell. 1983 Dec;35(2 Pt 1):457–465. doi: 10.1016/0092-8674(83)90179-4. [DOI] [PubMed] [Google Scholar]
  23. Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Walker M. D., Edlund T., Boulet A. M., Rutter W. J. Cell-specific expression controlled by the 5'-flanking region of insulin and chymotrypsin genes. Nature. 1983 Dec 8;306(5943):557–561. doi: 10.1038/306557a0. [DOI] [PubMed] [Google Scholar]
  25. Zinkernagel R. M., Doherty P. C. MHC-restricted cytotoxic T cells: studies on the biological role of polymorphic major transplantation antigens determining T-cell restriction-specificity, function, and responsiveness. Adv Immunol. 1979;27:51–177. doi: 10.1016/s0065-2776(08)60262-x. [DOI] [PubMed] [Google Scholar]

Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis

RESOURCES