The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1999/12/1717/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 11, December 6, 1999 1717-1722

Brief Definitive Report

Coupling and Uncoupling of Tumor Immunity and Autoimmunity

Wilbur B. Bownea,b, Roopa Srinivasana,b, Jedd D. Wolchoka,b, William G. Hawkinsa,b, Nathalie E. Blacherea,b, Ruben Dyalla,b, Jonathan J. Lewisa,b, and Alan N. Houghtona,b

a Memorial Sloan-Kettering Cancer Center, New York, New York 10021
b Weill Graduate School of Medical Sciences of Cornell University, New York, New York 10021
Swim Across America Laboratory, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021.212-794-4352212-639-7595

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) gp75TRP-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 gp75TRP-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 gp75TRP-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.

Key Words: melanoma • melanocyte • tyrosinase-related protein • T cell • perforin

W.B. Bowne and R. Srinivasan share first authorship on this paper.

© 1999 The Rockefeller University Press


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