Original Article

T Cells Compete for Access to Antigen-bearing Antigen-presenting Cells

Correspondence to: Ross M. Kedl, National Jewish Medical and Research Center, 5th Floor Goodman Bldg., K512, 1400 Jackson St., Denver, CO 80206. Tel:303-398-1465 Fax:303-398-1396

These studies tested whether antigenic competition between T cells occurs. We generated CD8⁺ T cell responses in H-2^b mice against the dominant ovalbumin epitope SIINFEKL (ova8) and subdominant epitope KRVVFDKL, using either vaccinia virus expressing ovalbumin (VV-ova) or peptide-pulsed dendritic cells. CD8⁺ T cell responses were visualized by major histocompatibility complex class I–peptide tetrameric molecules. Transfer of transgenic T cells with high affinity for ova8 (OT1 T cells) completely inhibited the response of host antigen-specific T cells to either antigen, demonstrating that T cells can directly compete with each other for response to antigen. OT1 cells also inhibited CD8⁺ T cell responses to an unrelated peptide, SIYRYGGL, providing it was presented on the same dendritic cells as ova8. These inhibitions were not due to a more rapid clearance of virus or antigen-presenting cells (APCs) by the OT1 cells. Rather, the inhibition was caused by competition for antigen and antigen-bearing cells, since it could be overcome by the injection of large numbers of antigen-pulsed dendritic cells. These results imply that common properties of T cell responses, such as epitope dominance and secondary response affinity maturation, are the result of competitive interactions between antigen-bearing APC and T cell subsets.

Key Words: T cell, competition, tetramer, antigen-presenting cell, dendritic cell

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• Probst, H. C., Dumrese, T., van den Broek, M. F. (2002). Cutting Edge: Competition for APC by CTLs of Different Specificities Is Not Functionally Important During Induction of Antiviral Responses. J. Immunol. 168: 5387-5391 [Abstract] [Full Text]  
• Yoneyama, H., Narumi, S., Zhang, Y., Murai, M., Baggiolini, M., Lanzavecchia, A., Ichida, T., Asakura, H., Matsushima, K. (2002). Pivotal Role of Dendritic Cell-derived CXCL10 in the Retention of T Helper Cell 1 Lymphocytes in Secondary Lymph Nodes. JEM 195: 1257-1266 [Abstract] [Full Text]  
• Palmowski, M. J., Choi, E. M.-L., Hermans, I. F., Gilbert, S. C., Chen, J.-L., Gileadi, U., Salio, M., Van Pel, A., Man, S., Bonin, E., Liljestrom, P., Dunbar, P. R., Cerundolo, V. (2002). Competition Between CTL Narrows the Immune Response Induced by Prime-Boost Vaccination Protocols. J. Immunol. 168: 4391-4398 [Abstract] [Full Text]  
• Rodriguez, F., Harkins, S., Slifka, M. K., Whitton, J. L. (2002). Immunodominance in Virus-Induced CD8+ T-Cell Responses Is Dramatically Modified by DNA Immunization and Is Regulated by Gamma Interferon. J. Virol. 76: 4251-4259 [Abstract] [Full Text]  
• Ge, Q., Palliser, D., Eisen, H. N., Chen, J. (2002). Homeostatic T cell proliferation in a T cell-dendritic cell coculture system. Proc. Natl. Acad. Sci. USA 10.1073/pnas.052714199v1 [Abstract] [Full Text]  
• Tawab, A., Fields, J., Chao, E., Kurlander, R. J. (2002). Recombinant lemA without adjuvant induces extensive expansion of H2-M3-restricted CD8 effectors, which can suppress primary listeriosis in mice. Int Immunol 14: 225-232 [Abstract] [Full Text]  
• Topham, D. J., Castrucci, M. R., Wingo, F. S., Belz, G. T., Doherty, P. C. (2001). The Role of Antigen in the Localization of Naive, Acutely Activated, and Memory CD8+ T Cells to the Lung During Influenza Pneumonia. J. Immunol. 167: 6983-6990 [Abstract] [Full Text]  
• Wang, Q., Strong, J., Killeen, N. (2001). Homeostatic Competition Among T Cells Revealed by Conditional Inactivation of the Mouse Cd4 Gene. JEM 194: 1721-1730 [Abstract] [Full Text]  
• Smith, S. G., Patel, P. M., Porte, J., Selby, P. J., Jackson, A. M. (2001). Human Dendritic Cells Genetically Engineered to Express a Melanoma Polyepitope DNA Vaccine Induce Multiple Cytotoxic T-Cell Responses. Clin. Cancer Res. 7: 4253-4261 [Abstract] [Full Text]  

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