T cells compete for access to antigen-bearing antigen-presenting cells

RM Kedl, WA Rees, DA Hildeman, B Schaefer… - The Journal of …, 2000 - rupress.org
RM Kedl, WA Rees, DA Hildeman, B Schaefer, T Mitchell, J Kappler, P Marrack
The Journal of experimental medicine, 2000rupress.org
These studies tested whether antigenic competition between T cells occurs. We generated
CD8+ T cell responses in H-2b 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 …
These studies tested whether antigenic competition between T cells occurs. We generated CD8+ T cell responses in H-2b 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.
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