Skip to main content

Advertisement

Log in

Effect of invariant chain on major histocompatibility complex class I molecule expression and stability on human breast tumor cell lines

  • Original Article
  • Published:
Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

Invariant chain (Ii) binds to the human leukocyte antigen (HLA) class II molecule and assists it in the process of peptide acquisition. In addition, Ii binds to the HLA class I molecule, although there has been little study of its effects on the HLA class I molecule. In addition to its normal expression on antigen-presenting cells, Ii expression is up regulated in a variety of tumors. By flow cytometric analysis, we found that expression of Ii resulted in an increase in the number of cell surface HLA class I molecules and in the proportion of unstable HLA class I molecules at the surface of breast tumor cell lines. These data suggest that the expression of Ii by tumor cells may quantitatively and qualitatively alter the presentation of antigens on those cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Aden DP, Fogel A, Plotkin S, Damjanov I, Knowles BB (1979) Controlled synthesis of HBsAg in a differentiated human liver carcinoma-derived cell line. Nature 282:615–616

    Article  PubMed  CAS  Google Scholar 

  2. Armstrong TD, Clements VK, Ostrand-Rosenberg S (1998) Class II-transfected tumor cells directly present endogenous antigen to CD4+T cells in vitro and are APCs for tumor-encoded antigens in vivo. J Immunother 21:218–224

    Article  PubMed  CAS  Google Scholar 

  3. Cailleau R, Olive M, Cruciger OV (1978) Long-term human breast carcinoma cell lines of metastatic origin: preliminary characterization. In Vitro 17:911–915

    Article  Google Scholar 

  4. Carreno BM, Hansen TH (1994) Exogenous peptide ligand influences the expression and half-life of free HLA class I heavy chains ubiquitously detected at the cell surface. Eur J Immunol 24:1285–1292

    Article  PubMed  CAS  Google Scholar 

  5. Cerundolo V, Elliott T, Elvin J, Bastin J, Townsend A (1992) Association of the human invariant chain with H-2Db class I molecules. Eur J Immunol 22:2243–2248

    Article  PubMed  CAS  Google Scholar 

  6. Cormier JN, Panelli MC, Hackett JA, Bettinotti MP, Mixon A, Wunderlich J, Parker LL, Restifo NP, Ferrone S, Marincola FM (1999) Natural variation of the expression of HLA and endogenous antigen modulates CTL recognition in an in vitro melanoma model. Int J Cancer 80:781–790

    Article  PubMed  CAS  Google Scholar 

  7. Cresswell P (1992) Chemistry and functional role of the invariant chain. Curr Opin Immunol 4:87–92

    Article  PubMed  CAS  Google Scholar 

  8. Dahiya R, Kwak KS, Byrd JC, Ho S, Yoon WH, Kim YS (1993) Mucin synthesis and secretion in various human epithelial cancer cell lines that express the MUC-1 mucin gene. Cancer Res 53:1437–1443

    PubMed  CAS  Google Scholar 

  9. De Silva AD, Boesteanu A, Song R, Nagy N, Harhaj E, Harding CV, Joyce S (1999) Thermolabile H-2 Kb molecules expressed by transporter associated with antigen processing-deficient RMA-S cells are occupied by low-affinity peptides. J Immunol 163:4413–4420

    PubMed  Google Scholar 

  10. Fogh J, Wright WC, Loveless JD (1977) Absence of HeLa cell contamination in 169 cell lines derived from human tumors. J Natl Cancer Inst 58:209–214

    PubMed  CAS  Google Scholar 

  11. Iwamura T, Katsuki T, Ide K (1987) Establishment and characterization of a human pancreatic cancer cell lines (SUIT-2) producing caricnoembryonic antigen and carbohydrate antigen 19–9. Jpn J Cancer Res 78:54–62

    PubMed  CAS  Google Scholar 

  12. Jabrane-Ferrat N, Faille A, Loiseau P, Poirier O, Charron D, Calvo F (1990) Effect of gamma interferon on HLA class-I and -II transcription and protein expression in human breast adenocarcinoma cell lines. Int J Cancer 45:1169–1176

    Article  PubMed  CAS  Google Scholar 

  13. Jiang Z, Xu M, Savas L, LeClair P, Banner BF (1999) Invariant chain expression in colon neoplasms. Virch Arch 435:32–36

    Article  CAS  Google Scholar 

  14. Keydar I, Chen L, Karby S, Weiss FR, Delarea J, Radu M, Chaitcik S, Brenner HJ (1979) Establishment and characterization of a cell line of human breast carcinoma origin. Eur J Cancer 15:659–670

    PubMed  CAS  Google Scholar 

  15. Koretz K, Moldenhauer G, Majdic O, Moller P (1989) Correlation of HLA-D/Ii antigen expression in breast carcinoma with local lymphohistiocytic infiltration reveals considerable dysregulation in a subset of tumors. Int J Cancer 44:816–822

    Article  PubMed  CAS  Google Scholar 

  16. Long EO, Rosen-Bronson S, Karp DR, Malnati M, Sekaly RP, Jaraquemada D (1991) Efficient cDNA expression vectors for stable and transient expression of HLA-DR in transfected fibroblasts and lymphoid cells. Hum Immunol 31:229–235

    Article  PubMed  CAS  Google Scholar 

  17. Moller P, Mattfeldt T, Gross C, Schlosshauer P, Koch A, Koretz K, Moldenhauer G, Kaufmann M, Otto HF (1989) Expression of HLA-A, -B, -C, -DR, -DP, -DQ, and of HLA-D-associated invariant chain (Ii) in non-neoplasmic mammary epithelium, fibroadenoma, adenoma, and carcinoma of the breast. Am J Pathol 135:73–83

    PubMed  CAS  Google Scholar 

  18. Moller P, Koretz K, Schlag P, Momburg, F (1991) Frequency of abnormal expression of HLA-A,B,C and HLA-DR molecules, invariant chain, and LFA-3 (CD58) in colorectal carcinoma and its impact on tumor recurrence. Int J Cancer (Suppl) 6:155–162

    Google Scholar 

  19. Nakabayashi H, Taketa K, Miyano K, Yamane T, Sato J (1982) Growth of human hepatoma cell lines with differentiated functions in chemically defined medium. Cancer Res 42:3858–3863

    PubMed  CAS  Google Scholar 

  20. Owens RB, Smith HS, Nelson-Rees WA, Springer EL (1976) Epithelial cell cultures from normal and cancerous human tissues. J Natl Cancer Inst 56:843–849

    PubMed  CAS  Google Scholar 

  21. Ozato K, Hansen TH, Sachs DH (1980) Monoclonal antibodies to mouse MHC antigens. II. Antibodies to the H-2Ld antigen, the product of a third polymorphic locus of the mouse major histocompatibility complex. J Immunol 125:2473–2477

    PubMed  CAS  Google Scholar 

  22. Parham P, Barnstable CJ, Bodmer WH (1979) Use of a monoclonal antibody (W6/32) in structural studies of HLA-A, B, C antigens. J Immunol 123:342–349

    PubMed  CAS  Google Scholar 

  23. Parham P, Brodsky FM (1981) Partial purification and some properties of BB7.2. A cytotoxic monoclonal antibody with specificity for HLA-A2 and a variant of HLA-A28. Hum Immunol 3:277–299

    Article  PubMed  CAS  Google Scholar 

  24. Powis SJ (2006) CLIP-region mediated interaction of Invariant chain with MHC class I molecules. FEBS Lett 580:3112–3116

    Article  PubMed  CAS  Google Scholar 

  25. Reber AJ, Turnquist HR, Thomas HJ, Lutz CT, Solheim JC (2002) Expression of invariant chain can cause an allele-dependent increase in the surface expression of MHC class I molecules. Immunogenetics 54:74–81

    Article  PubMed  CAS  Google Scholar 

  26. Ribas A, Timmerman JM, Butterfield LH, Economou JS (2003) Determinant spreading and tumor responses after peptide-based cancer immunotherapy. Trends Immunol 24:58–61

    Article  PubMed  CAS  Google Scholar 

  27. Ribas A, Glaspy JA, Lee Y, Dissette VB, Seja E, Vu HT, Tchekmedyian NS, Oseguera D, Comin-Anduix B, Wargo JA, Amarnani SN, McBride WH, Economou JS, Butterfield LH (2004) Role of dendritic cell phenotype, determinant spreading, and negative costimulatory blockade in dendritic cell-based melanoma immunotherapy. J Immunother 27:354–367

    Article  PubMed  CAS  Google Scholar 

  28. Rivoltini L, Baracchini KC, Viggiano V, Kawakami Y, Smith A, Mixon A, Restifo NP, Topalian SL, Simonis TB, Rosenberg SA, Marincola FM (1995) Quantitative correlation between HLA class I allele expression and recognition of melanoma cells by antigen specific cytotoxic T lymphocytes. Cancer Res 55:3149–3157

    PubMed  CAS  Google Scholar 

  29. Saito T, Kimura M, Kawasaki T, Sato S, Tomita Y (1997) MHC class II antigen-associated invariant chain on renal cell cancer may contribute to the anti-tumor immune response of the host. Cancer Lett 115:121–127

    Article  PubMed  CAS  Google Scholar 

  30. Soule HD, Vazquez J, Long A, Albert S, Brennan M (1973) A human cell line from a pleural effusion derived from a breast carcinoma. J Natl Cancer Inst 51:1409–1416

    PubMed  CAS  Google Scholar 

  31. Stam NJ, Spits H, Ploegh HL (1986) Monoclonal antibodies raised against denatured HLA-B locus heavy chains permit biochemical characterization of certain HLA-C locus products. J Immunol 137:2299–2306

    PubMed  CAS  Google Scholar 

  32. Stam NJ, Vroom TM, Peters PJ, Pastoors EB, Ploegh HL (1990) HLA-A- and HLA-B-specific monoclonal antibodies reactive with free heavy chains in western blots, in formalin-fixed, paraffin-embedded tissue sections and in cryo-immuno-electron microscopy. Int Immunol 2:113–125

    Article  PubMed  CAS  Google Scholar 

  33. Stone KR, Mickey DD, Wunderli H, Mickey GH, Paulson DF (1978) Isolation of a human prostate carcinoma cell line (DU 145). Int J Cancer 21:274–281

    Article  PubMed  CAS  Google Scholar 

  34. Sugita M, Brenner MB (1995) Association of the invariant chain with major histocompatibility complex class I molecules directs trafficking to endocytic compartments. J Biol Chem 270:1443–1448

    Article  PubMed  CAS  Google Scholar 

  35. Tsutsumida H, Swanson BJ, Singh PK, Caffrey TC, Kitajima S, Goto M, Yonezawa S, Hollingsworth MA (2006) RNA interference suppression of MUC1 reduces the growth rate and metastatic phenotype of human pancreatic cancer cells. Clin Cancer Res 12:2976–2987

    Article  PubMed  CAS  Google Scholar 

  36. Turnquist HR, Solheim JC (2001) Analysis of major histocompatibility complex class I interactions with endoplasmic reticulum proteins. Meth Mol Biol 156:165–173

    CAS  Google Scholar 

  37. Vezeridis MP, Meiner PA, Tibbetts LM, Doremus CM, Tzanakakis G, Calabresi P (1990) Heterogeneity of potential for hematogenous metastasis in a human pancreatic carcinoma. J Surg Res 48:51–55

    Article  PubMed  CAS  Google Scholar 

  38. Vigna JL, Smith KD, Lutz CT (1996) Invariant chain association with MHC class I. J Immunol 157:4503–4510

    PubMed  CAS  Google Scholar 

  39. Yewdell JW, Bennink JR (1989) Brefeldin A specifically inhibits presentation of protein antigens to cytotoxic T lymphocytes. Science 244:1072–1075

    Article  PubMed  CAS  Google Scholar 

  40. Young AN, Amin MB, Moreno CS, Lim SD, Cohen C, Petros JA, Marshall FF, Neish AS (2001) Expression profiling of renal epithelial neoplasms: a method for tumor classification and discovery of diagnostic molecular markers. Am J Pathol 158:1639–1651

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Austin Ahles for her assistance with this project. We also thank Dr. Shantaram Joshi, Dr. Kenneth Cowan, Dr. Vinod Labhasetwar, Dr. Michael A. Hollingsworth, Dr. Richard MacDonald, Christopher Connelly, Michelle Hartman, Jaspreet Vasir, Tom Caffrey, Dr. Pankaj Singh, Dr. Peter Cresswell and Dr. Ted Hansen for their assistance with obtaining cell lines, and Dr. Eric Long for the RSV.5neo Vector. We gratefully acknowledge the assistance of the personnel of the University of Nebraska Medical Center Cell Analysis Facility and the Monoclonal Antibody Facility. Core facilities at the University of Nebraska Medical Center receive support from the NIH/NCI Cancer Center Support Grant P30CA036727 (to the Eppley Cancer Center) and the Nebraska Research Initiative. This work was supported by NIH/NIGMS R01 Grant GM057428 and an LB506 Nebraska DHHS Cancer & Smoking Disease Research Grant (to J.C.S.), a Structural Biology and Biophysics Training Program Fellowship from the Department of Education Graduate Assistance in Areas of National Need Program (to H.L.C), NIH/NCI Training Grant T32 CA009476 Fellowship (to L.C.S.), UNMC Graduate Studies Fellowships (to L.C.S. and A.T.), NIH/NRSA Fellowship F32 AI055152 (to C.R.M.), and DOD Breast Cancer Training Program DAMD 17-00-1-0361 Fellowship (to A.J.R.).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Joyce C. Solheim.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lin, X., Wang, X., Capek, H.L. et al. Effect of invariant chain on major histocompatibility complex class I molecule expression and stability on human breast tumor cell lines. Cancer Immunol Immunother 58, 729–736 (2009). https://doi.org/10.1007/s00262-008-0595-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00262-008-0595-1

Keywords

Navigation