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• W2040360211 abstract "52 Indirect presentation of donor derived antigens in the context of recipient MHC occurs during acute and chronic allograft rejection. Previously published studies of the indirect pathway have predominantly focused on CD4 responses to MHC II restricted determinants. Processing and presentation of exogenously derived determinants can also occur through an alternative MHC I pathway, suggesting that graft rejection may prime an indirect response to CD8 T cells as well as to CD4 T cells. In order to test this hypothesis we made use of the fact that both H-2k female, and H-2b female mice reject male skin grafts and that dominant class I restricted determinants derived from the male H-Y antigen have been identified for each strain (HY peptide/k and HY peptide/b, respectively). Placement of male H-2b skin grafts onto (k x b)F1 female recipients resulted in graft rejection, and an expected HY peptide/b specific recall immune response was detected by IFNγ ELISA spot analysis. In addition, rejection of the male H-2b graft by the (k x b)F1 recipient primed an indirect response to HY peptide/k that was of similar magnitude and cytokine phenotype as the directly primed response. Importantly, the HY peptide/k determinant was not presented on the graft itself (as the graft was H-2b male-no expression of MHC I k), providing clear evidence that priming of an indirect response to a class I restricted determinant can occur during rejection. Analogous responses to HY peptide/b were detectable during rejection of H-2k grafts. If these indirectly primed CD8 cells functioned as memory cells in vivo, we hypothesized that they would mediate accelerated graft rejection. To address this question we primed the indirect CD8 response to HY peptide/b by first placing H-2k male skin grafts onto (k x b) F1 female recipients. We then determined how this indirectly primed response affected rejection of a subsequent male H-2b graft. Control mice were first primed with either H-2k female graft (not rejected) or no primary graft, followed by the same challenge with a male H-2b graft. Strikingly, indirect priming with a male H-2k skin graft resulted in accelerated rejection of an H-2b male graft compared to control groups (MST 13.4 d versus 16.5-17.4 d for control groups). These findings definitively show that indirect presentation of MHC I restricted determinants occurs during allograft rejection, and that the induced CD8 cells act as primed memory T cells." @default.
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• W2040360211 date "1999-04-01" @default.
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• W2040360211 title "INDIRECT PRIMING TO A CLASS I RESTRICTED EPITOPE ACCELERATES GRAFT REJECTION IN MICE" @default.
• W2040360211 doi "https://doi.org/10.1097/00007890-199904150-00080" @default.
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