High avidity CD8 + T cells generated from CD28-deficient or wildtype mice exhibit a differential dependence on lipid raft integrity for activation

Abstract

CD28 has been shown to play an important role in T cell activation. Among the downstream events associated with CD28 engagement is the reorganization of the cytoskeleton resulting in lipid raft aggregation. In our previous studies we investigated the involvement of lipid rafts in the activation of high avidity CD8 + T lymphocytes, which recognize cells bearing very low levels of peptide antigen, versus low avidity cells, which require high levels of peptide antigen. In these studies we found that high avidity cells were much more sensitive to lipid raft disruption compared to low avidity cells. Given the important role for CD28 in lipid raft reorganization and our previous finding that high avidity cells are extremely dependent on lipid raft integrity, we hypothesized that high avidity cells could not be generated in the absence of CD28. Surprisingly, we have found that the absence of CD28 does not alter the ability to generate high or low avidity CD8 + T cells. In fact high and low avidity lines generated in parallel from CD28-deficient and WT mice exhibited very similar requirements for peptide antigen. We next compared the effect of lipid raft disruption on the activation of high versus low avidity cells from CD28-deficient and WT mice. While high avidity cells generated from WT mice exhibited the expected dependence on lipid raft integrity, high avidity cells from CD28-deficient mice were not affected. These data suggest that the lines generated from the CD28-deficient mice have developed alternative strategies to promote high sensitivity to peptide antigen.