Competition between T cells was shown in vivo using transgenic T cells in adoptive-transfer experiments. T cells with the OT1 T-cell receptor (TCR) specific for an ovalbumin (OVA) peptide were transferred into non-transgenic animals, and the mice were challenged with dendritic cells (DCs) loaded with OVA. OVA–MHC tetramers were used to assess the response of the endogenous T cells — the transferred OT1 T cells almost completely blocked the host T-cell response. The group then evaluated the ability of high- and low-affinity T cells, generated in vivo, to modulate host T-cell responses. C57BL/6 mice were challenged with OVA-expressing vaccinia virus and left to rest for 25 days to allow a memory response to develop. Transfer of high-affinity T cells followed by challenge with OVA-pulsed DCs resulted in almost complete inhibition of the host T-cell response, but transfer of low-affinity T cells produced much less inhibition. The competition between cells of the same peptide–MHC specificity was more efficient than competition between T cells with differing specificity.
Next, Kedl and colleagues examined whether removal of MHC–peptide complexes from the APC surface had a role in T-cell competition. DCs from GFP (green fluorescent protein) transgenic mice were pulsed with OVA and transferred intradermally into C57/BL6 mice. A monoclonal antibody was used to measure the amount of OVA–MHC expressed on DCs after transfer in the presence or absence of OT1 T cells. When OT1 T cells were co-transferred, expression of OVA–MHC on the DC surface decreased rapidly and was virtually undetectable after 48 hours.
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