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Original Article

^a Cancer Research Institute, Denver, Colorado 80206
^b Howard Hughes Medical Institute, Denver, Colorado 80206
^c Department of Immunology, National Jewish Medical and Research Center and University of Colorado Health Sciences Center, Denver, Colorado 80206
^d Department of Biochemistry and Molecular Genetics, Denver, Colorado 80206
^e Department of Pharmacology, Denver, Colorado 80206
^f Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80206
National Jewish Medical and Research Center, 5th Floor Goodman Bldg., K512, 1400 Jackson St., Denver, CO 80206.303-398-1396303-398-1465

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

© 2000 The Rockefeller University Press

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