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Resistance to herpes stromal keratitis conferred by an lgG2a-derived peptide

Nature volume 376, pages 431–434 (1995)Cite this article

Abstract

NOT all peripheral tissue antigens enter the thymus and it is unclear how the immune system remains tolerant to this class of self antigen. As tolerance to self peptides can generate gaps in the T-cell repertoire for cross-reactive foreign antigens1,2, we investigated whether this mechanism might also diminish autoimmune reactions to similar peptides expressed by peripheral tissues. Herpes stromal keratitis (HSK) is a virally induced autoimmune reaction against corneal tissues mediated by T cells3á¤-5, and is a leading cause of human blindness6. Resistance to HSK in mice is associated with allotypic variation in immunoglobulin genes7,8, possibly because circulating immunoglobin-derived peptides can cross-tolerize T cells specific for corneal tissue autoantigens. Here we show that HSK is mediated by T-cell clones specific for corneal self antigens which also recognize an allotype-bearing peptide derived from IgG2a, and that exposure of HSK-susceptible mice to a soluble form of this peptide confers resistance to HSK. Shared expression of peptide subsequences between sequestered tissue proteins and circulating proteins may be important for maintenance of self-tolerance and prevention of autoimmunity.

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Affiliations

  1. Department of Pathology, Harvard Medical School, Laboratory of Immunopathology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts, 02115, USA

    Anne C. Avery, Zi-Shan Zhao & Harvey Cantor

  2. Hilles Immunology Laboratory, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, 243 Charles Street, Boston, Massachusetts, 02114, USA

    Alejandro Rodriguez, Masoud Soheilian & C. Stephen Foster

  3. Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, Massachusetts, 02138, USA

    Elizabeth K. Bikoff

Authors
  1. Anne C. Avery
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  2. Zi-Shan Zhao
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  3. Alejandro Rodriguez
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  4. Elizabeth K. Bikoff
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  5. Masoud Soheilian
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  6. C. Stephen Foster
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  7. Harvey Cantor
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Avery, A., Zhao, ZS., Rodriguez, A. et al. Resistance to herpes stromal keratitis conferred by an lgG2a-derived peptide. Nature 376, 431–434 (1995). https://doi.org/10.1038/376431a0

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