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

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Kurts, C; Heath, WR; Carbone, FR; Allison, J; Miller, JFAP; Kosaka, HDate
1996-09-01Source Title
Journal of Experimental MedicinePublisher
ROCKEFELLER UNIV PRESSAffiliation
Microbiology and ImmunologyMetadata
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Kurts, C., Heath, W. R., Carbone, F. R., Allison, J., Miller, J. F. A. P. & Kosaka, H. (1996). Constitutive class I-restricted exogenous presentation of self antigens in vivo. JOURNAL OF EXPERIMENTAL MEDICINE, 184 (3), pp.923-930. https://doi.org/10.1084/jem.184.3.923.Access Status
Open AccessAbstract
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.
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