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. 1986 May;83(9):2949–2953. doi: 10.1073/pnas.83.9.2949

Qa gene expression: biosynthesis and secretion of Qa-2 molecules in activated T cells.

M J Soloski, J Vernachio, G Einhorn, A Lattimore
PMCID: PMC323424  PMID: 3486423

Abstract

The biosynthesis and expression of the tissue-specific class I molecule Qa-2 have been studied in resting and activated T-cell populations. Polyclonal activation of T lymphocytes induces a 3- to 4-fold increase in the biosynthesis of Qa-2 molecules but no increase in cell-surface levels. Analysis of the biosynthetic pathway of the Qa-2 molecule in activated lymphocytes reveals that approximately equal to 70% of the newly synthesized Qa-2 molecules are secreted as soluble molecules. In resting-cell populations, Qa-2 remains entirely cell-associated. This process is unique to the Qa-2 molecule, since other class I molecules (e.g., H-2Kb and H-2Db) synthesized by activated cells remain cell-associated. The possibility that the secreted Qa-2 molecule is the product of a new Qa gene or an alternatively spliced mRNA is considered. These results indicate that the Qa-2 molecules may not just function as a cell-surface recognition structure but also may serve a role as a soluble factor synthesized by activated lymphoid cell populations.

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Selected References

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  1. Cook R. G., Jenkins R. N., Flaherty L., Rich R. R. The Qa-1 alloantigens. II. Evidence for the expression of two Qa-1 molecules by the Qa-1d genotype and for cross-reactivity between Qa-1 and H-2K. J Immunol. 1983 Mar;130(3):1293–1299. [PubMed] [Google Scholar]
  2. Devlin J. J., Lew A. M., Flavell R. A., Coligan J. E. Secretion of a soluble class I molecule encoded by the Q10 gene of the C57BL/10 mouse. EMBO J. 1985 Feb;4(2):369–374. doi: 10.1002/j.1460-2075.1985.tb03638.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Emerson S. G., Cone R. E. I-Kk and H-2Kk antigens are shed as supramolecular particles in association with membrane lipids. J Immunol. 1981 Aug;127(2):482–486. [PubMed] [Google Scholar]
  4. Emerson S. G., Murphy D. B., Cone R. E. Selective turnover and shedding of H-2K and H-2D antigens is controlled by the major histocompatibility complex. Implications for H-2-restricted recognition. J Exp Med. 1980 Oct 1;152(4):783–795. doi: 10.1084/jem.152.4.783. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Hoessli D., Rungger-Brändle E. Association of specific cell-surface glycoproteins with a triton X-100-resistant complex of plasma membrane proteins isolated from T-lymphoma cells (P1798). Exp Cell Res. 1985 Jan;156(1):239–250. doi: 10.1016/0014-4827(85)90278-2. [DOI] [PubMed] [Google Scholar]
  6. Hogarth P. M., Basten A., Prichard-Briscoe H., Henning M. H., Sutton V. R., McKenzie I. F. The distribution of the Qa-2 alloantigen on functional T lymphocytes. J Immunol. 1985 Sep;135(3):1632–1636. [PubMed] [Google Scholar]
  7. Hogarth P. M., Crewther P. E., McKenzie I. F. Description of a Qa-2 like alloantigen (Qa-m2). Eur J Immunol. 1982 May;12(5):374–379. doi: 10.1002/eji.1830120504. [DOI] [PubMed] [Google Scholar]
  8. Iványi D., Cherry M., Démant P. Molecular heterogeneity of D-end products detected by anti-H-2.28 sera. III. Reactivity of certain anti-H-2.28 alloantisera with Qa-2 antigen. Immunogenetics. 1982;15(5):477–484. doi: 10.1007/BF00345907. [DOI] [PubMed] [Google Scholar]
  9. Jones P. P. Analysis of H-2 and Ia antigens by two-dimensional polyacrylamide gel electrophoresis. Methods Enzymol. 1984;108:452–466. doi: 10.1016/s0076-6879(84)08111-8. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Koch G. L., Smith M. J. An association between actin and the major histocompatibility antigen H-2. Nature. 1978 May 25;273(5660):274–278. doi: 10.1038/273274a0. [DOI] [PubMed] [Google Scholar]
  12. Kress M., Glaros D., Khoury G., Jay G. Alternative RNA splicing in expression of the H-2K gene. Nature. 1983 Dec 8;306(5943):602–604. doi: 10.1038/306602a0. [DOI] [PubMed] [Google Scholar]
  13. Kress M., Glaros D., Khoury G., Jay G. Alternative RNA splicing in expression of the H-2K gene. Nature. 1983 Dec 8;306(5943):602–604. doi: 10.1038/306602a0. [DOI] [PubMed] [Google Scholar]
  14. Kvist S., Peterson P. A. Isolation and partial characterization of a beta2-microglobulin-containing, H-2 antigen-like murine serum protein. Biochemistry. 1978 Oct 31;17(22):4794–4801. doi: 10.1021/bi00615a029. [DOI] [PubMed] [Google Scholar]
  15. Lalanne J. L., Cochet M., Kummer A. M., Gachelin G., Kourilsky P. Different exon-intron organization at the 5' part of a mouse class I gene is used to generate a novel H-2Kd-related mRNA. Proc Natl Acad Sci U S A. 1983 Dec;80(24):7561–7565. doi: 10.1073/pnas.80.24.7561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lalanne J. L., Transy C., Guerin S., Darche S., Meulien P., Kourilsky P. Expression of class I genes in the major histocompatibility complex: identification of eight distinct mRNAs in DBA/2 mouse liver. Cell. 1985 Jun;41(2):469–478. doi: 10.1016/s0092-8674(85)80020-9. [DOI] [PubMed] [Google Scholar]
  17. Mellor A. L., Antoniou J., Robinson P. J. Structure and expression of genes encoding murine Qa-2 class I antigens. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5920–5924. doi: 10.1073/pnas.82.17.5920. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Natori T., Tanigaki N., Pressman D. A mouse plasma substance carrying beta2-microglobulin activity and lacking in H-2 alloantigenic activity. J Immunogenet. 1976 Apr;3(2):123–134. doi: 10.1111/j.1744-313x.1976.tb00563.x. [DOI] [PubMed] [Google Scholar]
  19. Noelle R., Krammer P. H., Ohara J., Uhr J. W., Vitetta E. S. Increased expression of Ia antigens on resting B cells: an additional role for B-cell growth factor. Proc Natl Acad Sci U S A. 1984 Oct;81(19):6149–6153. doi: 10.1073/pnas.81.19.6149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. O'Farrell P. H. High resolution two-dimensional electrophoresis of proteins. J Biol Chem. 1975 May 25;250(10):4007–4021. [PMC free article] [PubMed] [Google Scholar]
  21. Ramanathan L., Rogers M. J., Robinson E. A., Hearing V. J., Tanigaki N., Appella E. Biochemical analysis of a 40,000 mol. wt mouse serum protein which binds beta 2-microglobulin and has serological cross-reactivity with H-2 antigens. Mol Immunol. 1982 Sep;19(9):1075–1086. doi: 10.1016/0161-5890(82)90318-2. [DOI] [PubMed] [Google Scholar]
  22. Sharrow S. O., Flaherty L., Sachs D. H. Serologic cross-reactivity between Class I MHC molecules and an H-2-linked differentiation antigen as detected by monoclonal antibodies. J Exp Med. 1984 Jan 1;159(1):21–40. doi: 10.1084/jem.159.1.21. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Soloski M. J., Uhr J. W., Flaherty L., Vitetta E. S. Qa-2, H-2K, and H-2D alloantigens evolved from a common ancestral gene. J Exp Med. 1981 May 1;153(5):1080–1093. doi: 10.1084/jem.153.5.1080. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Steinmetz M., Winoto A., Minard K., Hood L. Clusters of genes encoding mouse transplantation antigens. Cell. 1982 Mar;28(3):489–498. doi: 10.1016/0092-8674(82)90203-3. [DOI] [PubMed] [Google Scholar]
  25. Straus D. S., Stroynowski I., Schiffer S. G., Hood L. Expression of hybrid class I genes of the major histocompatibility complex in mouse L cells. Proc Natl Acad Sci U S A. 1985 Sep;82(18):6245–6249. doi: 10.1073/pnas.82.18.6245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Stroynowski I., Forman J., Goodenow R. S., Schiffer S. G., McMillan M., Sharrow S. O., Sachs D. H., Hood L. Expression and T cell recognition of hybrid antigens with amino-terminal domains encoded by Qa-2 region of major histocompatibility complex and carboxyl termini of transplantation antigens. J Exp Med. 1985 May 1;161(5):935–952. doi: 10.1084/jem.161.5.935. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Vitetta E. S., Artzt K., Bennett D., Boyse E. A., Jacob F. Structural similarities between a product of the T/t-locus isolated from sperm and teratoma cells, and H-2 antigens isolated from splenocytes. Proc Natl Acad Sci U S A. 1975 Aug;72(8):3215–3219. doi: 10.1073/pnas.72.8.3215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Weiss E. H., Golden L., Fahrner K., Mellor A. L., Devlin J. J., Bullman H., Tiddens H., Bud H., Flavell R. A. Organization and evolution of the class I gene family in the major histocompatibility complex of the C57BL/10 mouse. Nature. 1984 Aug 23;310(5979):650–655. doi: 10.1038/310650a0. [DOI] [PubMed] [Google Scholar]
  29. Winoto A., Steinmetz M., Hood L. Genetic mapping in the major histocompatibility complex by restriction enzyme site polymorphisms: most mouse class I genes map to the Tla complex. Proc Natl Acad Sci U S A. 1983 Jun;80(11):3425–3429. doi: 10.1073/pnas.80.11.3425. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Wysocki L. J., Sato V. L. "Panning" for lymphocytes: a method for cell selection. Proc Natl Acad Sci U S A. 1978 Jun;75(6):2844–2848. doi: 10.1073/pnas.75.6.2844. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Yuan D., Vitetta E. S., Kettman J. R. Cell surface immunoglobulin. XX. Antibody responsiveness of subpopulations of B lymphocytes bearing different isotypes. J Exp Med. 1977 Jun 1;145(6):1421–1435. doi: 10.1084/jem.145.6.1421. [DOI] [PMC free article] [PubMed] [Google Scholar]

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