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. 1995 Nov 1;182(5):1615–1619. doi: 10.1084/jem.182.5.1615

Strictly transporter of antigen presentation (TAP)-dependent presentation of an immunodominant cytotoxic T lymphocyte epitope in the signal sequence of a virus protein

PMCID: PMC2192180  PMID: 7595234

Abstract

Peptides presented by major histocompatibility complex (MHC) class I molecules are derived from intracellularly synthesized proteins. Cytosolic proteins are fragmented into peptides, which are subsequently transported via the transporter of antigen presentation (TAP) into the endoplasmic reticulum (ER), where they bind to MHC class I molecules. We have investigated the requirements for MHC class I presentation of the immunodominant gp33 cytotoxic T lymphocyte epitope of the lymphocytic choriomeningitis virus. This epitope is located within the leader peptide of the virus glycoprotein. Such an epitope is expected to be presented in a TAP-independent manner, since it is released into the ER by signal peptidase. Taking advantage of TAP1-/- mice, however, we show both in vitro and in vivo that, after virus infection, the presentation of the gp33 epitope is strictly dependent on a functional TAP heterodimer. The results are discussed with respect to peptide trimming processes in the ER.

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Selected References

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  1. Anderson K., Cresswell P., Gammon M., Hermes J., Williamson A., Zweerink H. Endogenously synthesized peptide with an endoplasmic reticulum signal sequence sensitizes antigen processing mutant cells to class I-restricted cell-mediated lysis. J Exp Med. 1991 Aug 1;174(2):489–492. doi: 10.1084/jem.174.2.489. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bruns M., Cihak J., Müller G., Lehmann-Grube F. Lymphocytic choriomeningitis virus. VI. Isolation of a glycoprotein mediating neutralization. Virology. 1983 Oct 15;130(1):247–251. doi: 10.1016/0042-6822(83)90135-6. [DOI] [PubMed] [Google Scholar]
  3. Buchmeier M. J., Zinkernagel R. M. Immunodominant T cell epitope from signal sequence. Science. 1992 Aug 21;257(5073):1142–1142. doi: 10.1126/science.257.5073.1142. [DOI] [PubMed] [Google Scholar]
  4. Esquivel F., Yewdell J., Bennink J. RMA/S cells present endogenously synthesized cytosolic proteins to class I-restricted cytotoxic T lymphocytes. J Exp Med. 1992 Jan 1;175(1):163–168. doi: 10.1084/jem.175.1.163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Falk K., Rötzschke O., Rammensee H. G. Cellular peptide composition governed by major histocompatibility complex class I molecules. Nature. 1990 Nov 15;348(6298):248–251. doi: 10.1038/348248a0. [DOI] [PubMed] [Google Scholar]
  6. Gabathuler R., Reid G., Kolaitis G., Driscoll J., Jefferies W. A. Comparison of cell lines deficient in antigen presentation reveals a functional role for TAP-1 alone in antigen processing. J Exp Med. 1994 Oct 1;180(4):1415–1425. doi: 10.1084/jem.180.4.1415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Henderson R. A., Michel H., Sakaguchi K., Shabanowitz J., Appella E., Hunt D. F., Engelhard V. H. HLA-A2.1-associated peptides from a mutant cell line: a second pathway of antigen presentation. Science. 1992 Mar 6;255(5049):1264–1266. doi: 10.1126/science.1546329. [DOI] [PubMed] [Google Scholar]
  8. Hosken N. A., Bevan M. J. An endogenous antigenic peptide bypasses the class I antigen presentation defect in RMA-S. J Exp Med. 1992 Mar 1;175(3):719–729. doi: 10.1084/jem.175.3.719. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Lemke H., Hämmerling G. J., Hämmerling U. Fine specificity analysis with monoclonal antibodies of antigens controlled by the major histocompatibility complex and by the Qa/TL region in mice. Immunol Rev. 1979;47:175–206. doi: 10.1111/j.1600-065x.1979.tb00293.x. [DOI] [PubMed] [Google Scholar]
  10. Momburg F., Roelse J., Hämmerling G. J., Neefjes J. J. Peptide size selection by the major histocompatibility complex-encoded peptide transporter. J Exp Med. 1994 May 1;179(5):1613–1623. doi: 10.1084/jem.179.5.1613. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Morgan G. M., Dellos H., McKenzie I. F., Melvold R. W., Bailey D. W. Studies of two H-2Db mutants: B6. C-H-2bm13 and B6.C-H-2bm14. Immunogenetics. 1980;11(4):341–349. doi: 10.1007/BF01567801. [DOI] [PubMed] [Google Scholar]
  12. Ohashi P. S., Zinkernagel R. M., Leuscher I., Hengartner H., Pircher H. Enhanced positive selection of a transgenic TCR by a restriction element that does not permit negative selection. Int Immunol. 1993 Feb;5(2):131–138. doi: 10.1093/intimm/5.2.131. [DOI] [PubMed] [Google Scholar]
  13. Pircher H., Moskophidis D., Rohrer U., Bürki K., Hengartner H., Zinkernagel R. M. Viral escape by selection of cytotoxic T cell-resistant virus variants in vivo. Nature. 1990 Aug 16;346(6285):629–633. doi: 10.1038/346629a0. [DOI] [PubMed] [Google Scholar]
  14. Pircher H., Ohashi P. S., Boyd R. L., Hengartner H., Brduscha K. Evidence for a selective and multi-step model of T cell differentiation: CD4+CD8low thymocytes selected by a transgenic T cell receptor on major histocompatibility complex class I molecules. Eur J Immunol. 1994 Sep;24(9):1982–1987. doi: 10.1002/eji.1830240907. [DOI] [PubMed] [Google Scholar]
  15. Powis S. J., Townsend A. R., Deverson E. V., Bastin J., Butcher G. W., Howard J. C. Restoration of antigen presentation to the mutant cell line RMA-S by an MHC-linked transporter. Nature. 1991 Dec 19;354(6354):528–531. doi: 10.1038/354528a0. [DOI] [PubMed] [Google Scholar]
  16. Rammensee H. G., Falk K., Rötzschke O. Peptides naturally presented by MHC class I molecules. Annu Rev Immunol. 1993;11:213–244. doi: 10.1146/annurev.iy.11.040193.001241. [DOI] [PubMed] [Google Scholar]
  17. Rock K. L., Gramm C., Rothstein L., Clark K., Stein R., Dick L., Hwang D., Goldberg A. L. Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules. Cell. 1994 Sep 9;78(5):761–771. doi: 10.1016/s0092-8674(94)90462-6. [DOI] [PubMed] [Google Scholar]
  18. Roelse J., Grommé M., Momburg F., Hämmerling G., Neefjes J. Trimming of TAP-translocated peptides in the endoplasmic reticulum and in the cytosol during recycling. J Exp Med. 1994 Nov 1;180(5):1591–1597. doi: 10.1084/jem.180.5.1591. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Sanders S. L., Schekman R. Polypeptide translocation across the endoplasmic reticulum membrane. J Biol Chem. 1992 Jul 15;267(20):13791–13794. [PubMed] [Google Scholar]
  20. Schumacher T. N., Kantesaria D. V., Heemels M. T., Ashton-Rickardt P. G., Shepherd J. C., Fruh K., Yang Y., Peterson P. A., Tonegawa S., Ploegh H. L. Peptide length and sequence specificity of the mouse TAP1/TAP2 translocator. J Exp Med. 1994 Feb 1;179(2):533–540. doi: 10.1084/jem.179.2.533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Snyder H. L., Yewdell J. W., Bennink J. R. Trimming of antigenic peptides in an early secretory compartment. J Exp Med. 1994 Dec 1;180(6):2389–2394. doi: 10.1084/jem.180.6.2389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Townsend A., Ohlén C., Bastin J., Ljunggren H. G., Foster L., Kärre K. Association of class I major histocompatibility heavy and light chains induced by viral peptides. Nature. 1989 Aug 10;340(6233):443–448. doi: 10.1038/340443a0. [DOI] [PubMed] [Google Scholar]
  23. Van Kaer L., Ashton-Rickardt P. G., Ploegh H. L., Tonegawa S. TAP1 mutant mice are deficient in antigen presentation, surface class I molecules, and CD4-8+ T cells. Cell. 1992 Dec 24;71(7):1205–1214. doi: 10.1016/s0092-8674(05)80068-6. [DOI] [PubMed] [Google Scholar]
  24. Wallny H. J., Rötzschke O., Falk K., Hämmerling G., Rammensee H. G. Gene transfer experiments imply instructive role of major histocompatibility complex class I molecules in cellular peptide processing. Eur J Immunol. 1992 Mar;22(3):655–659. doi: 10.1002/eji.1830220307. [DOI] [PubMed] [Google Scholar]
  25. Wei M. L., Cresswell P. HLA-A2 molecules in an antigen-processing mutant cell contain signal sequence-derived peptides. Nature. 1992 Apr 2;356(6368):443–446. doi: 10.1038/356443a0. [DOI] [PubMed] [Google Scholar]
  26. Zhou X., Glas R., Momburg F., Hämmerling G. J., Jondal M., Ljunggren H. G. TAP2-defective RMA-S cells present Sendai virus antigen to cytotoxic T lymphocytes. Eur J Immunol. 1993 Aug;23(8):1796–1801. doi: 10.1002/eji.1830230810. [DOI] [PubMed] [Google Scholar]
  27. Zinkernagel R. M., Leist T., Hengartner H., Althage A. Susceptibility to lymphocytic choriomeningitis virus isolates correlates directly with early and high cytotoxic T cell activity, as well as with footpad swelling reaction, and all three are regulated by H-2D. J Exp Med. 1985 Dec 1;162(6):2125–2141. doi: 10.1084/jem.162.6.2125. [DOI] [PMC free article] [PubMed] [Google Scholar]

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