Self peptide/MHC class I complexes have a negligible effect on the response of some CD8+ T cells to foreign antigen

MHC molecules loaded with self peptides do not trigger a T cell immune response but may deliver signals important for peripheral T cell survival and function. It is unclear if self peptide/MHC complexes on APC in addition can influence the T cell response to co-presented foreign ligands. To address this question, TAP-sufficient and TAP-deficient cells were loaded with ovalbumin peptide (pOVA) to generate APC that present pOVA/H-2Kb complexes in the context of high or low levels of self peptide-loaded MHC class I, respectively. The two cell types were then used to stimulate different CD8+ T cells specific for ovalbumin while the number of presented pOVA/H-2Kb complexes was independently assessed by staining with 25-D1, an antibody against pOVA/H-2Kb. In each case, T cell activation was independent of TAP expression by the APC and depended exclusively on the amount of 25-D1 staining. We conclude that the number of pOVA/Kb complexes and not their frequency relative to self peptide/MHC complexes determines the response of those T cells tested here. These results imply that the repertoire of self peptide/MHC class I complexes presented by APC has a negligible effect on the response of some CD8+ T cells to foreign ligands.