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Title

Direct presentation of a melanocyte-associated antigen in peripheral lymph nodes induces cytotoxic CD8+ T cells

Authors
Schuler, Prisca
Beermann, Friederich
Donda, Alena
French, L E.
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Published in Cancer research. 2008, vol. 68, no. 20, p. 8410-8
Abstract Encounter of self-antigens in the periphery by mature T cells induces tolerance in the steady-state. Hence, it is not understood why the same peripheral antigens are also promiscuously expressed in the thymus to mediate central tolerance. Here, we analyzed CD8(+) T-cell tolerance to such an antigen constituted by ovalbumin under the control of the tyrosinase promoter. As expected, endogenous CD8(+) T-cell responses were altered in the periphery of transgenic mice, resulting from promiscuous expression of the self-antigen in mature medullary epithelial cells and deletion of high-affinity T cells in the thymus. In adoptive T-cell transfer experiments, we observed constitutive presentation of the self-antigen in peripheral lymph nodes. Notably, this self-antigen presentation induced persisting cytotoxic cells from high-affinity CD8(+) T-cell precursors. Lymph node resident melanoblasts expressing tyrosinase directly presented the self-antigen to CD8(+) T cells, independently of bone marrow-derived antigen-presenting cells. This peripheral priming was independent of the subcellular localization of the self-antigen, indicating that this mechanism may apply to other melanocyte-associated antigens. Hence, central tolerance by promiscuous expression of peripheral antigens is a mandatory, rather than a superfluous, mechanism to counteract the peripheral priming, at least for self-antigens that can be directly presented in lymph nodes. The peripheral priming by lymph node melanoblasts identified here may constitute an advantage for immunotherapies based on adoptive T-cell transfer.
Keywords AnimalsAntigen PresentationAutoantigens/immunologyImmunotherapyLymph Nodes/immunologyMelanocytes/immunologyMelanoma/therapyMiceMice, Inbred C57BLMice, Inbred DBAOvalbumin/genetics/immunologyT-Lymphocytes, Cytotoxic/immunology
Identifiers
PMID: 18922914
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Other version: http://cancerres.aacrjournals.org/cgi/content/full/68/20/8410
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Research group Pathologie et immunologie (906)
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SCHULER, Prisca et al. Direct presentation of a melanocyte-associated antigen in peripheral lymph nodes induces cytotoxic CD8+ T cells. In: Cancer research, 2008, vol. 68, n° 20, p. 8410-8. https://archive-ouverte.unige.ch/unige:1404

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Deposited on : 2009-04-27

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