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

doi:10.1084/jem.184.3.923

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

C Kurts, WR Heath, FR Carbone, J Allison, JF Miller and H Kosaka
Thymus Biology Unit, Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.

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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Koido, S., Tanaka, Y., Chen, D., Kufe, D., Gong, J. (2002). The Kinetics of In Vivo Priming of CD4 and CD8 T Cells by Dendritic/Tumor Fusion Cells in MUC1-Transgenic Mice. J. Immunol. 168: 2111-2117 [Abstract] [Full Text]
Mintern, J. D., Davey, G. M., Belz, G. T., Carbone, F. R., Heath, W. R. (2002). Cutting Edge: Precursor Frequency Affects the Helper Dependence of Cytotoxic T Cells. J. Immunol. 168: 977-980 [Abstract] [Full Text]
Zhang, Y., O'Brien, B., Trudeau, J., Tan, R., Santamaria, P., Dutz, J. P. (2002). In Situ {beta} Cell Death Promotes Priming of Diabetogenic CD8 T Lymphocytes. J. Immunol. 168: 1466-1472 [Abstract] [Full Text]
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Topham, D. J., Castrucci, M. R., Wingo, F. S., Belz, G. T., Doherty, P. C. (2001). The Role of Antigen in the Localization of Naive, Acutely Activated, and Memory CD8+ T Cells to the Lung During Influenza Pneumonia. J. Immunol. 167: 6983-6990 [Abstract] [Full Text]
Leishman, A. J., Naidenko, O. V., Attinger, A., Koning, F., Lena, C. J., Xiong, Y., Chang, H.-C., Reinherz, E., Kronenberg, M., Cheroutre, H. (2001). T Cell Responses Modulated Through Interaction Between CD8alpha alpha and the Nonclassical MHC Class I Molecule, TL. Science 294: 1936-1939 [Abstract] [Full Text]