LOSS OF A UNIQUE TUMOR-ANTIGEN BY CYTOTOXIC T-LYMPHOCYTE IMMUNOSELECTION FROM A 3-METHYLCHOLANTHRENE-INDUCED MOUSE SARCOMA REVEALS SECONDARY UNIQUE AND SHARED ANTIGENS

Most chemically induced tumors of mice express unique antigens that ca ll be recognized by cytotoxic T lymphocytes (CTL) and thereby mediate tumor rejection. The number of different antigens expressed by a singl e tumor and their interplay during immunization and rejection are larg ely unexplored. We used CTL clones specific to individual tumor antige ns to examine the number and distribution of CTL antigens expressed by cell lines derived from 3-methylcholanthrene-induced sarcomas of (C57 BL/6J x SPRET/Ei)F-1 mice. Each tumor cell line expressed one or more antigens that were unique, that is, not detected on cell lines from in dependent sarcomas. Immunoselection against an immunodominant antigen produced both major histocompatibility complex class I antigen and uni que tumor antigen loss variants. Immunization of mice with antigen-neg ative immunoselected variants resulted in CTL that recognized addition al antigens that wire also expressed by the progenitor tumor. Some CTL recognized additional unique tumor antigen(s); other CTL recognized a shared antigen expressed not only by the immunizing cell line, but al so by independent sarcoma cell lines and untransformed myoblastoid cel l Lines. CTL that recognized tile shared antigen were also recovered f rom mice immunized in vivo with an untransformed myoblastoid cell line . These findings support a model of immunodominance among chemically i nduced tumor antigens in which shared antigens are masked by unique im munodominant antigens.