Analysis of the Major Histocompatibility Complex Class I Antigen Presentation Machinery in Human Lung Cancer

  • Kim, Hyun-Pyo (Graduate School of Biotechnology, Korea University) ;
  • Jin, Mi-Rim (Graduate School of Biotechnology, Korea University) ;
  • Kim, Ick-Young (Graduate School of Biotechnology, Korea University) ;
  • Ahn, Byung-Yoon (Graduate School of Biotechnology, Korea University) ;
  • Kang, Seong-Man (Graduate School of Biotechnology, Korea University) ;
  • Choi, Eui-Ju (Graduate School of Biotechnology, Korea University) ;
  • Kim, Joon (Graduate School of Biotechnology, Korea University) ;
  • Kim, Ik-Hwan (Graduate School of Biotechnology, Korea University) ;
  • Ahn, Kwang-Seog (Graduate School of Biotechnology, Korea University)
  • Published : 1999.06.01

Abstract

Tumor cells may alter the expression of proteins involved in antigen processing and presentation, allowing them to avoid recognition and elimination by cytotoxic T cells. In order to investigate whether the major histocompatibility complex (MHC) class I-mediated antigen processing machinery is preserved in human lung cancer cell lines, we examined the expression of multiple components of the MHC class I antigen processing pathway, including transporter associated with antigen processing (TAP), $\beta_2$-microglobulin, MHC class I molecules, and chaperones which have not been previously examined in this context. Row cytometry analysis showed that the cell surface expression of MHC class I molecules was downregulated in all of the cell lines. While some cell lines showed no detectable expression of MHC class I molecules, pulse-chase experiments showed that MHC class I molecules were synthesized in the other cell lines but not transported from the endoplasmic reticulum to the cell surface. Low or nondetectable levels of TAP1 and/or TAP2 expression were demonstrated by Western blot analysis in all of the cell lines, representing a variety of lung tissue types. In some cases, this was accompanied by loss of tapasin expression. Our findings suggest that downregulation of antigen processing may be one of the strategies used by tumors to escape immune surveillance. This study provides further information for designing the potential therapeutic applications such as immunotherapy and gene therapy against cancers.

Keywords

References

  1. Immunity v.6 The ERluminal domain of the HCMV glycoprotein US6 inhibits peptide translocation by TAP Ahn, K.;A. Gruhler;B. Galocha;T. R. Jones;E. Wiertz;H. Ploegh;P. Peterson;Y. Yang;K. Fruh
  2. Cell v.43 Impaired intracellular transport of class I MHC antigens as a possible means for adenoviruses to evade immune surveillance Anderson, M.;S. Paabo;T. Nilsson;P. A. Peterson
  3. Proc. Natl. Acad. Sci. USA v.89 Altered binding of regulatory factors to HLA class I enhancer sequence in human tumor cell lines lacking class I antigen expression Blanchet, O.;J.-F. Bourge;H. Zinszner;A. Israel;P. Kourilsky;J. Dausset;L. Degos;P. Paul
  4. J. Exp. Med. v.183 Human tumor antigens recognized by T lymphocytes Boon, T.;P. Van der Bruggen
  5. Can. Res. v.54 Expression of HLA-A, B, C antigens in primary and metastatic tumor cell populations of human carcinomas Cordon-Cardo, C.;Z. Fuks;M. Drobnjak;C. Moreno;L. Eisenbach;M. Feldmann
  6. J. Exp. Med. v.179 Loss of transporter protein encoded by the TAP-1 gene is highly correlated with loss of HLA expression in cervical carcinomas Cromme, F. V.;J. Airey;M. T. Heemels;H. L. Ploegh;P. J. Keating;P. L. Stern;C. L. M. Meijer;J. M. M. Walboomers
  7. Immunol. Today v.16 Loss of HLA class I antigens by melanoma cells: Molecular mechanisms, functional significance and clinical relevance Ferrone, S.;F. Marincola
  8. J. Exp. Med. v.177 Tumorigenicity conferred to lymphoma mutant by major histocompatibility complex-encoded transporter gene Franksson, L.;E. Georges;S. Powis;G. Butcher;J. Howard;K. Karre
  9. Nature v.357 Proteolysis, proteasomes and antigen presentation Goldberg, A. L.;K. L. Rock
  10. Trends Cell Biol. v.7 Calnexin, calreticulin and the folding of glycoproteins Helenius, A.;E. S. Trombetta;D. N. Herbert;J. F. Simons
  11. Nature v.355 Assembly and function of two ABC transporter proteins encoded in the human major histocompatibility complex Kelly, A.;S. H. Powis;L. A. Kerr;I. Mockridge;T. Elliot;J. Bastin;B. Uchanska-Ziegler;A. Ziegler;J. Trowsdale;A. Townsend
  12. Immunol. Today v.12 Modulation of MHC antigen expression by viruses and oncogenes Mausdley, D. J.;J. S. Pound
  13. Science v.261 Selective and ATP-dependent translocation of peptides by MHC-encoded transporter Neefjes, J. J.;F. Momburg;G. J. Hammerling
  14. J. Exp. Med. v.181 Species-specific difference in chaperone interaction of human and mouse major histocompatibility complex class I molecules Noessner, E.;P. Parham
  15. Science v.277 A critical role for tapasin in the assembly and function of multimeric MHC class ITAP complexes Ortmann, B.;J. Copeman;P. J. Lehner;B. Sadasivan;J. A. Herberg;A. G. Grandea;S. R. Riddell;R.Tampe;T. Spies;J. Trowsdale;P. Cresswell
  16. Nature v.354 Restoration of antigen presentation to the mutant cell line RMA-S by an MHC-linked transporter Powis, S. J.;A. R. Townsend;E. V. Deverson;J. Bastin;G. W. Butcher;J. C. Howard
  17. J. Exp. Med. v.177 Identification of human cancers deficient in antigen processing Restifo, N. P.;F. Esquivel;Y. Kawakami;J. W. Yewdell;J. J. Mule;S. A. Rosenberg;J. R. Bennink
  18. J. Exp. Med. v.180 Down-regulation of peptide transporter genes in cell lines transformed with highly oncogenic adenovirus12 Roterm-Yeduhar,R.;S. Winograd;S. Sela;J. E. Coligan;R. Ehrlich
  19. Eur. J. Immunol. v.25 Restoration of endogenous antigen processing in Burkitt's lymphoma cells by Epstein-Barr virus latent membrane protein-1:Coordinate upregulation of peptide transporters and HLA-class I antigen expression Rowe, M.;R. Khanna;C. Jacob
  20. Immunity v.5 Role for calreticulin and a novel glycoprotein, tapasin, in the interaction of MHC class 1 molecules with TAP Sadasivan, B.;P. J. Lehner;B. Ortmann;T. Spies;P. Cresswell
  21. J. Immunol. v.152 Resistance to natural killer cell lysis conferred by TAP1/2 genes in human antigen-processing mutant cells Salcedo, M.;F. Momburg;G. H. Hammerling;H.-G. Ljunggren
  22. J. Natl. Cancer Inst. v.87 Molecular characterization of defective antigen processing in human prostate cancer Sanda, M. G.;N. P. Restifio;J. C. Walsh;Y. Kawakami;W. G. Nelson;D. M. Pardoll;J. W. Simons
  23. J. Immunol. v.158 Prominence of beta2-microglobulin, class I heavy chain conformation, and tapasin in the interaction of class I heavy chain with calreticulin and the transporter associated with antigen processing Solhcim, J. C.;M. R. Harris;C. S. Kindle;T. H. Hansen
  24. Nature v.348 A gene in the human major histocompatibility complex class II region controlling the class I antigen presentation pathway Spies, T.;M. Bresnahan;S. Bahram;D. Arnold;G. Blanck;E. Mellins
  25. Science v.264 Interaction of MHC class I molecules with the transporter associated with antigen processing Suh, W.-K.;M. F. Cohen-Doyle;K. Fruh;K. Wang;P. A. Peterson;D. B. Williams
  26. Cur. Opin. Immunol. v.5 Regulation of MHC gene expression Ting, J. P.;A. S. Baldwin
  27. Cell v.42 Cytotoxic T cells recognize fragments of the influenza protein Townsend, A. R. M.;F. M. Gotchi;J. Davey
  28. Nature v.348 Sequences encoded in the class II region of the MHC related to the 'ABC' superfamily of transporters Trowsdale, J.;I. Hanson;L. Mockridge;S. Beck;A. Townsend;A. Kelly
  29. Canc. Res. v.53 Selective down-regulated expression of MHC class I alleles in human solid tumors Vegh, Z.;P. Wang. F. Vanky;E. Klein
  30. Annu. Rev. Immunol. v.14 Antigen processing and presentation by the class I major histocompatibility complex York, I. A.;K. L. Rock
  31. Nature v.396 Proto-oncogene PML controls gene devoted to MHS class I antigen presentation Zheng, P.;Y. Guo;Q. Niu;D. E. Levy;J. A. Dyck;S. Lu;L. A. Sheiman;Y. Liu