Kedl R M, Rees W A, Hildeman D A, Schaefer B, Mitchell T, Kappler J, Marrack P
Cancer Research Institute, National Jewish Medical and Research Center Denver, Colorado 80206, USA.
J Exp Med. 2000 Oct 16;192(8):1105-13. doi: 10.1084/jem.192.8.1105.
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.
这些研究检测了T细胞之间是否存在抗原竞争。我们使用表达卵清蛋白的痘苗病毒（VV-ova）或肽脉冲树突状细胞，在H-2(b)小鼠中诱导针对显性卵清蛋白表位SIINFEKL（ova8）和隐性表位KRVVFDKL的CD8(+) T细胞应答。通过主要组织相容性复合体I类-肽四聚体分子观察CD8(+) T细胞应答。转入对ova8具有高亲和力的转基因T细胞（OT1 T细胞）完全抑制了宿主抗原特异性T细胞对任何一种抗原的应答，表明T细胞可直接相互竞争以对抗原产生应答。OT1细胞也抑制了CD8(+) T细胞对不相关肽SIYRYGGL的应答，前提是该肽与ova8呈递于同一树突状细胞上。这些抑制作用并非由于OT1细胞更快地清除病毒或抗原呈递细胞（APC）。相反，抑制是由对抗原和携带抗原的细胞的竞争所致，因为大量注射抗原脉冲树突状细胞可克服这种抑制。这些结果提示，T细胞应答的共同特性，如表位优势和二次应答亲和力成熟，是携带抗原的APC与T细胞亚群之间竞争性相互作用的结果。
