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Research Article Free access | 10.1172/JCI4004

Tumor immunity and autoimmunity induced by immunization with homologous DNA.

L W Weber, W B Bowne, J D Wolchok, R Srinivasan, J Qin, Y Moroi, R Clynes, P Song, J J Lewis, and A N Houghton

The Swim Across America Laboratory, Sloan-Kettering Division, Cornell University Graduate School of Medical Sciences, New York 10021, USA.

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The Swim Across America Laboratory, Sloan-Kettering Division, Cornell University Graduate School of Medical Sciences, New York 10021, USA.

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The Swim Across America Laboratory, Sloan-Kettering Division, Cornell University Graduate School of Medical Sciences, New York 10021, USA.

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The Swim Across America Laboratory, Sloan-Kettering Division, Cornell University Graduate School of Medical Sciences, New York 10021, USA.

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The Swim Across America Laboratory, Sloan-Kettering Division, Cornell University Graduate School of Medical Sciences, New York 10021, USA.

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The Swim Across America Laboratory, Sloan-Kettering Division, Cornell University Graduate School of Medical Sciences, New York 10021, USA.

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The Swim Across America Laboratory, Sloan-Kettering Division, Cornell University Graduate School of Medical Sciences, New York 10021, USA.

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The Swim Across America Laboratory, Sloan-Kettering Division, Cornell University Graduate School of Medical Sciences, New York 10021, USA.

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The Swim Across America Laboratory, Sloan-Kettering Division, Cornell University Graduate School of Medical Sciences, New York 10021, USA.

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The Swim Across America Laboratory, Sloan-Kettering Division, Cornell University Graduate School of Medical Sciences, New York 10021, USA.

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Published September 15, 1998 - More info

Published in Volume 102, Issue 6 on September 15, 1998
J Clin Invest. 1998;102(6):1258–1264. https://doi.org/10.1172/JCI4004.
© 1998 The American Society for Clinical Investigation
Published September 15, 1998 - Version history
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Abstract

The immune system can recognize self antigens expressed by cancer cells. Differentiation antigens are prototypes of these self antigens, being expressed by cancer cells and their normal cell counterparts. The tyrosinase family proteins are well characterized differentiation antigens recognized by antibodies and T cells of patients with melanoma. However, immune tolerance may prevent immunity directed against these antigens. Immunity to the brown locus protein, gp75/ tyrosinase-related protein-1, was investigated in a syngeneic mouse model. C57BL/6 mice, which are tolerant to gp75, generated autoantibodies against gp75 after immunization with DNA encoding human gp75 but not syngeneic mouse gp75. Priming with human gp75 DNA broke tolerance to mouse gp75. Immunity against mouse gp75 provided significant tumor protection. Manifestations of autoimmunity were observed, characterized by coat depigmentation. Rejection of tumor challenge required CD4(+) and NK1.1(+) cells and Fc receptor gamma-chain, but depigmentation did not require these components. Thus, immunization with homologous DNA broke tolerance against mouse gp75, possibly by providing help from CD4(+) T cells. Mechanisms required for tumor protection were not necessary for autoimmunity, demonstrating that tumor immunity can be uncoupled from autoimmune manifestations.

Version history
  • Version 1 (September 15, 1998): No description
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