Abstract
Abstract CD1-restricted T cells are a unique subset of T cells that respond to lipid self- and foreign antigens presented by group 1 CD1 (CD1a, -b, -c) and group 2 CD1 (CD1-d) antigen presenting molecules. Previous studies have shown that group 1 CD1-restricted T cells can respond to lipid antigens derived from Mycobacterium tuberculosis. As group 1 CD1 molecules can accommodate a variety of lipid species, we sought to address whether group 1 CD1-restricted T cells can be activated by Staphylococcus aureus (SA) lipids. Using a transgenic mouse strain that expresses human group 1 CD1 molecules (hCD1Tg), it was found that group 1 CD1-restricted T cell responses against SA lipids can be observed in immunization and infection settings. When DCs coated with total lipid from MRSA strain USA300 were injected into hCD1Tg mice, lymphocytes produced significantly higher amounts of IFN-g in response to SA lipid in a group 1 CD1-dependent manner. Lymphocytes from SA-infected animals also produced more IL-17 in a group 1 CD1- and SA lipid antigen-dependent manner. Finally, long-term cultured CTL clones derived from immunized and infected animals displayed specificity toward SA lipid antigens. These clones produced IL-10 and TNF-α in response to SA lipid, demonstrating that group 1 CD1-restricted T cells isolated from immunized or infected animals can produce multiple cytokines in response to SA lipid.
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