Constitutive class I-restricted exogenous presentation of self antigens in vivo.

TLDR

The authors injected OT‑I CD8⁺ T cells into RIP‑mOVA mice and used unilateral nephrectomy and bone‑marrow chimeras to demonstrate that bone‑marrow–derived antigen‑presenting cells in draining lymph nodes present membrane‑bound OVA to the T cells. OT‑I cells accumulated and activated in the kidney and pancreas draining lymph nodes, showing that tissue‑associated self antigens can be presented via an exogenous class‑I pathway by short‑lived bone‑marrow APCs, constitutively priming T cells to non‑lymphoid tissue antigens.

Abstract

Ovalbumin (OVA)-specific CD8+ T cells from the T cell receptor-transgenic line OT-I (OT-I cells) were injected into unirradiated transgenic 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 phenotype and a proportion entered cell cycle. Unilateral nephrectomy 7-13 d before inoculation of OT-I cells into RIP-mOVA mice allowed the injected 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 histocompatibility haplotype incapable of presenting OVA to OT-I cells, no homing or activation was detectable. Therefore, OT-I cells were activated by OVA presented by short-lived antigen-presenting cells of bone marrow origin present in the draining LN of OVA-expressing tissue. These results provide the first evidence that tissue-associated "self" antigens can be presented in the context of class I via an exogenous processing pathway. This offers a constitutive mechanism whereby T cells can be primed to antigens that are present in nonlymphoid tissues, which are not normally surveyed by recirculating naive T cells.