CONSTITUTIVE CLASS I-RESTRICTED EXOGENOUS PRESENTATION OF SELF-ANTIGENS IN-VIVO

Ovalbumin (OVA)-specific CD8(+) T cells from the T cell receptor-trans genic line OT-I (OT-I cells) were injected into unirradiated transgeni c RIP-mOVA mice, which express a membrane-bound form of OVA (mOVA) in the pancreatic islet beta cells and the renal proximal tubular cells. OT-I cells accumulated in the draining lymph nodes (LN) of the kidneys and pancreas and in no other LN. They displayed an activated phenotyp e and a proportion entered cell cycle. Unilateral nephrectomy 7-13 d b efore inoculation of OT-I cells into RIP-mOVA mice allowed the injecte d T cells to home only to the regional LN of the remaining kidney (and pancreas), but when the operation was performed 4 h before injecting the T cells, homing to the LN of the excised kidney was evident. When the bone marrow of RIP-mOVA mice was replaced with one of a major hist ocompatibility haplotype incapable of presenting OVA to OT-I cells, no homing or activation was detectable. Therefore, OT-I cells were activ ated by OVA presented by short-lived antigen-presenting cells of bone marrow origin present in the draining LN of OVA-expressing tissue. The se results provide the first evidence that tissue-associated ''self'' antigens can be presented in the context of class I via an exogenous p rocessing pathway. This offers a constitutive mechanism whereby T cell s can be primed to antigens that are present in nonlymphoid tissues, w hich are not normally surveyed by recirculating naive T cells.