Identification of a unique tumor-specific antigen as a novel class I major histocompatibility molecule

C. Philipps, M. McMillan, P. M. Flood, D. B. Murphy, J. Forman, D. Lancki, J. E. Womack, R. S. Goodenow, H. Schreiber

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

Cancers induced by physical or chemical carcinogens express tumor-specific antigens that are uniquely specific for any given tumor; therefore, there is a seemingly endless variety of these unique antigens. We have studied a UV-induced fibrosarcoma, designated 1591, to elucidate the obscure molecular nature and genetic origins of unique tumor specific antigens. A monoclonal antibody raised against syngeneic 1591 tumor cells has unique tumor specificity. This tumor-specific monoclonal antibody precipitated from the tumor a 45-kDa molecule associated with a 12-kDa molecule having a pI of β2-microglobulin. This and other evidence indicated that the 1591 tumor expresses a novel class I molecule. A 1591 variant selected for the absence of binding to the monoclonal antibody lacked the novel class I MHC molecule as well as reactivity with cytotoxic T lymphocytes specific for the 1591 tumor. Furthermore, tumor cells bearing the antigen are rejected while variants that have lost the antigen grow progressively. Fourteen of 14 host-selected progressor tumor variants lost reactivity with the monoclonal antibody and provided further evidence that this novel class I molecule is a transplantation antigen on the parental 1591 tumor required for immune rejection. The identification of a unique tumor-specific antigen as a novel class I major histocompatibility complex gene product allows us to search for the possible genetic mechanisms involved and to explore further the role such molecules play in tumor immunity and malignancy.

Original languageEnglish (US)
Pages (from-to)5140-5144
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume82
Issue number15
DOIs
StatePublished - Dec 1 1985

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