Journal of Experimental Medicine, Vol 178, 933-940, Copyright © 1993 by Rockefeller University Press

ARTICLES

A tumor escape variant that has lost one major histocompatibility complex class I restriction element induces specific CD8+ T cells to an antigen that no longer serves as a target

S Seung, JL Urban and H Schreiber
Department of Pathology, University of Chicago, Illinois 60637.

After loss of expression of a major histocompatibility complex class I Kk allele, the escape variant of an immunogenic tumor grows progressively in normal mice. This progressor variant is resistant to killing by cytotoxic T lymphocytes (CTLs) directed against the A and B antigens presented by Kk. Although the variant retains the expression of the Dk allele and is sensitive to CTLs directed against the C antigen presented by Dk, the variant failed to induce CTLs to this antigen in vivo. Instead, the variant induced CD8+ T cells directed to the A antigen. This was shown at the molecular level by T cell receptor beta chain sequence analysis of the responding cells. Further evidence for the presence of A antigen in the variant came from the finding that spleen cells of mice injected intraperitoneally with the variant tumor cells were primed for an anti-A CD8+ CTL response in vivo. Thus, in contrast to other variants that lost a target antigen and induced a CTL response to remaining target antigens, the Kk loss variant continued to induce an immune response to a tumor antigen that is no longer presented on the tumor cell surface. Even though the variant escapes in a single step because an effective CTL response to secondary antigens is prevented, these secondary antigens remain as potential targets of immunotherapy on the variant's cell surface.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Morandi, F., Levreri, I., Bocca, P., Galleni, B., Raffaghello, L., Ferrone, S., Prigione, I., Pistoia, V. (2007). Human Neuroblastoma Cells Trigger an Immunosuppressive Program in Monocytes by Stimulating Soluble HLA-G Release. Cancer Res. 67: 6433-6441 [Abstract] [Full Text]  
• Jenkinson, S. R., Williams, N. A., Morgan, D. J. (2005). The Role of Intercellular Adhesion Molecule-1/LFA-1 Interactions in the Generation of Tumor-Specific CD8+ T Cell Responses. J. Immunol. 174: 3401-3407 [Abstract] [Full Text]  
• Yu, P., Spiotto, M. T., Lee, Y., Schreiber, H., Fu, Y.-X. (2003). Complementary Role of CD4+ T Cells and Secondary Lymphoid Tissues for Cross-presentation of Tumor Antigen to CD8+ T Cells. J. Exp. Med. 197: 985-995 [Abstract] [Full Text]  
• Curti, A., Parenza, M., Colombo, M. P. (2003). Autologous and MHC class I-negative allogeneic tumor cells secreting IL-12 together cure disseminated A20 lymphoma. Blood 101: 568-575 [Abstract] [Full Text]  
• Igney, F. H., Krammer, P. H. (2002). Immune escape of tumors: apoptosis resistance and tumor counterattack. J. Leukoc. Biol. 71: 907-920 [Abstract] [Full Text]  
• Qin, Z., Harders, C., Cao, X., Huber, C., Blankenstein, T., Seliger, B. (2002). Increased Tumorigenicity, but Unchanged Immunogenicity, of Transporter for Antigen Presentation 1-deficient Tumors. Cancer Res. 62: 2856-2860 [Abstract] [Full Text]  
• van Mierlo, G. J. D., den Boer, A. Th., Medema, J. P., van der Voort, E. I. H., Fransen, M. F., Offringa, R., Melief, C. J. M., Toes, R. E. M. (2002). CD40 stimulation leads to effective therapy of CD40- tumors through induction of strong systemic cytotoxic T lymphocyte immunity. Proc. Natl. Acad. Sci. USA 99: 5561-5566 [Abstract] [Full Text]  
• Medema, J. P., de Jong, J., Peltenburg, L. T. C., Verdegaal, E. M. E., Gorter, A., Bres, S. A., Franken, K. L. M. C., Hahne, M., Albar, J. P., Melief, C. J. M., Offringa, R. (2001). Blockade of the granzyme B/perforin pathway through overexpression of the serine protease inhibitor PI-9/SPI-6 constitutes a mechanism for immune escape by tumors. Proc. Natl. Acad. Sci. USA 10.1073/pnas.201398198v1 [Abstract] [Full Text]  
• Nelson, D. J., Mukherjee, S., Bundell, C., Fisher, S., van Hagen, D., Robinson, B. (2001). Tumor Progression Despite Efficient Tumor Antigen Cross-Presentation and Effective "Arming" of Tumor Antigen-Specific CTL. J. Immunol. 166: 5557-5566 [Abstract] [Full Text]  
• Wang, Z., Marincola, F. M., Rivoltini, L., Parmiani, G., Ferrone, S. (1999). Selective Histocompatibility Leukocyte Antigen (HLA)-A2 Loss Caused by Aberrant Pre-mRNA Splicing in 624MEL28 Melanoma Cells. J. Exp. Med. 190: 205-216 [Abstract] [Full Text]  
• Toes, R. E.M., Ossendorp, F., Offringa, R., Melief, C. J.M. (1999). CD4 T Cells and Their Role in Antitumor Immune Responses. J. Exp. Med. 189: 753-756 [Full Text]  
• Sing, A. P., Ambinder, R. F., Hong, D. J., Jensen, M., Batten, W., Petersdorf, E., Greenberg, P. D. (1997). Isolation of Epstein-Barr Virus (EBV)-Specific Cytotoxic T Lymphocytes That Lyse Reed-Sternberg Cells: Implications for Immune-Mediated Therapy of EBV+ Hodgkin's Disease. Blood 89: 1978-1986 [Abstract] [Full Text]  
• Huang, A., Golumbek, P, Ahmadzadeh, M, Jaffee, E, Pardoll, D, Levitsky, H (1994). Role of bone marrow-derived cells in presenting MHC class I-restricted tumor antigens. Science 264: 961-965 [Abstract]  
• van Mierlo, G. J. D., den Boer, A. Th., Medema, J. P., van der Voort, E. I. H., Fransen, M. F., Offringa, R., Melief, C. J. M., Toes, R. E. M. (2002). CD40 stimulation leads to effective therapy of CD40- tumors through induction of strong systemic cytotoxic T lymphocyte immunity. Proc. Natl. Acad. Sci. USA 99: 5561-5566 [Abstract] [Full Text]  
• Medema, J. P., de Jong, J., Peltenburg, L. T. C., Verdegaal, E. M. E., Gorter, A., Bres, S. A., Franken, K. L. M. C., Hahne, M., Albar, J. P., Melief, C. J. M., Offringa, R. (2001). Blockade of the granzyme B/perforin pathway through overexpression of the serine protease inhibitor PI-9/SPI-6 constitutes a mechanism for immune escape by tumors. Proc. Natl. Acad. Sci. USA 98: 11515-11520 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS