Coupling and uncoupling of tumor immunity and autoimmunity.

Abstract

Self-antigens, in the form of differentiation antigens, are commonly recognized by the immune system on melanoma and other cancers. We have shown previously that active immunization of mice against the melanocyte differentiation antigen, a tyrosinase-related protein (TRP) gp75(TRP-1) (the brown locus protein) expressed by melanomas, could induce tumor immunity and autoimmunity manifested as depigmentation. In this system, tumor immunity and autoimmunity were mediated by autoantibodies. Here, we characterize immunity against another tyrosinase family glycoprotein TRP-2 (the slaty locus protein), using the same mouse model and method of immunization. As observed previously for gp75(TRP-1), immunity was induced by DNA immunization against a xenogeneic form of TRP-2, but not against the syngeneic gene, and depended on CD4(+) cells. Immunization against TRP-2 induced autoantibodies and autoreactive cytotoxic T cells. In contrast to immunization against gp75(TRP-1), both tumor immunity and autoimmunity required CD8(+) T cells, but not antibodies. Only autoimmunity required perforin, whereas tumor immunity proceeded in the absence of perforin. Thus, immunity induced against two closely related autoantigens that are highly conserved throughout vertebrate evolution involved qualitatively different mechanisms, i.e., antibody versus CD8(+) T cell. However, both pathways led to tumor immunity and identical phenotypic manifestations of autoimmunity.

• Authors: W B Bowne, R Srinivasan, J D Wolchok, W G Hawkins, N E Blachere, R Dyall, J J Lewis, A N Houghton
• Journal: The Journal of experimental medicine (J Exp Med) Vol. 190 Issue 11 Pg. 1717-22 (Dec 06 1999) ISSN: 0022-1007 [Print] United States
• PMID: 10587362 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Autoantibodies
• Membrane Glycoproteins
• Pore Forming Cytotoxic Proteins
• beta 2-Microglobulin
• Perforin
• Intramolecular Oxidoreductases
• dopachrome isomerase

Topics

• Animals
• Antibody Formation
• Autoantibodies (immunology)
• Female
• Humans
• Immunotherapy
• Intramolecular Oxidoreductases (genetics, immunology)
• Killer Cells, Natural (immunology)
• Lung Neoplasms (immunology, prevention & control, secondary)
• Lymphocyte Depletion
• Melanoma, Experimental (immunology, pathology, prevention & control)
• Membrane Glycoproteins (deficiency, genetics, physiology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Neoplasm Transplantation
• Perforin
• Pore Forming Cytotoxic Proteins
• T-Lymphocytes, Cytotoxic (immunology)
• Transfection
• Transplantation, Heterologous
• Transplantation, Isogeneic
• Tumor Cells, Cultured
• beta 2-Microglobulin (deficiency, genetics, physiology)