Tumor immunity and autoimmunity induced by immunization with homologous DNA Journal Article
| Authors: | Weber, L. W.; Bowne, W. B.; Wolchok, J. D.; Srinivasan, R.; Qin, J.; Moroi, Y.; Clynes, R.; Song, P.; Lewis, J. J.; Houghton, A. N. |
| Article Title: | Tumor immunity and autoimmunity induced by immunization with homologous DNA |
| 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 γ-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. |
| Keywords: | controlled study; nonhuman; proteins; animal cell; mouse; animals; mice; animal tissue; melanoma; tumor markers, biological; animal experiment; animal model; mice, inbred c57bl; hair color; immunological tolerance; immune tolerance; dna; antigens; antigens, neoplasm; cancer vaccines; membrane glycoproteins; antigen recognition; cd4-positive t-lymphocytes; vaccination; dna, neoplasm; melanoma, experimental; killer cells, natural; tumor immunity; fc receptor; autoimmunity; receptors, igg; monophenol monooxygenase; cd4 antigen; protein family; autoantibody; tumor rejection; oxidoreductases; vaccines, dna; autoantibodies; glycoprotein; antigens, surface; differentiation; tolerance; differentiation antigen; immunization; depigmentation; lectins, c-type; tyrosinase; xenogeneic; humans; female; priority journal; article |
| Journal Title: | Journal of Clinical Investigation |
| Volume: | 102 |
| Issue: | 6 |
| ISSN: | 0021-9738 |
| Publisher: | American Society for Clinical Investigation |
| Date Published: | 1998-09-15 |
| Start Page: | 1258 |
| End Page: | 1264 |
| Language: | English |
| PUBMED: | 9739060 |
| PROVIDER: | scopus |
| PMCID: | PMC509109 |
| DOI: | 10.1172/JCI4004 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 12 December 2016 -- Source: Scopus |
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