_:b29869 "of antigens represents normal tissue differentiation proteins because they are expressed in melanoma, normal melanocytes, and pigmented retinal cells, and are typified by the proteins tyrosinase (2, 3), TRP-1 (4), gp100 (6), and MART-1 (>>5<<). Some tumors were also found to express a mutated version of a normal cellular protein which forms a \u201Cforeign\u201D MHC-binding peptide specifically recognized by T cells." . . _:b29873 "The Lewis lung carcinoma expresses a mutated form of the connexin 37 protein which is recognized by CD8+ T cells restricted by H2-Kb (>>22<<). In the present paper, the first murine tumor\u2013associated antigen recognized by CD8+ T cells representing a normal tissue differentiation protein has been identified. As was the case with human gp100 and MART-1, a T cell line with known" . . _:b206744726 "4"^^ . _:b206744722 "6"^^ . . . . _:b206744723 "6"^^ . . _:b206744761 . . _:b29862 "One group of antigens, characterized by the MAGE (13, >>14<<), BAGE (15), and GAGE (16) families of proteins, are coded for by normal nonmutated genes, and seem to be expressed by tumor cell, testis, and sometimes placenta, but not other normal tissues." . _:b206744733 "3"^^ . . _:b206744732 "3"^^ . . _:b206744755 . _:b206744735 "3"^^ . _:b206744734 "3"^^ . . _:b206744786 . _:b206744814 . _:b29860 . _:b29861 . _:b206744729 "3"^^ . . _:b206744728 "3"^^ . _:b206744752 . _:b29854 "The locations and sizes of the five fragments are compared to the composite cDNA sequence of TRP-2 reported by I. Jackson et al. (>>8<<) in Fig. 2." . _:b206744738 . _:b206744727 . _:b206744730 . _:b206744766 . _:b206744731 "3"^^ . . _:b206744730 "3"^^ . _:b206744724 . _:b29866 "Another major family of antigens represents normal tissue differentiation proteins because they are expressed in melanoma, normal melanocytes, and pigmented retinal cells, and are typified by the proteins tyrosinase (2, >>3<<), TRP-1 (4), gp100 (6), and MART-1 (5)." . _:b29859 "In the last five years, much progress has been made in the molecular identification of tumor cell proteins which are recognized by the cellular immune system in the context of the MHC (4\u20136, >>11<<, 12). Work performed largely with patients with melanoma has identified nearly a dozen tumorassociated antigens which can be divided into several general categories." . _:b206744741 "2"^^ . _:b206744767 . _:b206744740 "3"^^ . _:b206744811 . _:b206744800 . _:b206744772 . . . _:b29852 . _:b206744743 "2"^^ . . _:b29862 . _:b206744742 "2"^^ . _:b29870 "This category of mutated tumor-associated antigen is exemplified by both \u03B2-catenin (with a serine to phenylalanine mutation at position 37; reference >>11<<), and the mutated form of cyclin-dependant kinase 4 (17)." . _:b206744737 "3"^^ . _:b206744725 . . _:b29858 "In the last five years, much progress has been made in the molecular identification of tumor cell proteins which are recognized by the cellular immune system in the context of the MHC (>>4<<\u20136, 11, 12). Work performed largely with patients with melanoma has identified nearly a dozen tumorassociated antigens which can be divided into several general categories." . _:b206744736 "3"^^ . _:b206744724 . _:b206744739 "3"^^ . _:b206744727 . _:b206744738 "3"^^ . . _:b206744726 . _:b206744749 "2"^^ . . . _:b206744748 "2"^^ . . . _:b206744751 "2"^^ . _:b206744723 . _:b29864 . _:b206744789 . _:b206744799 . _:b206744750 "2"^^ . . _:b206744722 . _:b206744745 "2"^^ . _:b206744733 . . _:b206744744 "2"^^ . _:b206744732 . _:b206744798 . _:b206744747 "2"^^ . _:b206744735 . _:b206744733 . _:b29872 . _:b206744746 "2"^^ . _:b206744808 . . _:b206744734 . _:b206744757 "2"^^ . _:b206744729 . . _:b206744778 . _:b29857 _:b29858 . _:b206744756 "2"^^ . _:b206744728 . _:b29857 _:b29859 . . _:b29857 _:b29860 . _:b206744737 . _:b29857 _:b29861 . _:b29857 _:b29862 . _:b206744809 . _:b206744759 "2"^^ . _:b206744731 . _:b206744771 . _:b29857 _:b29863 . _:b29857 _:b29864 . _:b29872 . _:b29857 _:b29865 . . _:b29857 _:b29866 . _:b206744758 "2"^^ . . _:b29857 _:b29867 . _:b206744730 . _:b29857 _:b29868 . _:b29857 _:b29869 . _:b29871 "This category of mutated tumor-associated antigen is exemplified by both \u03B2-catenin (with a serine to phenylalanine mutation at position 37; reference 11), and the mutated form of cyclin-dependant kinase 4 (>>17<<)." . _:b29857 _:b29870 . _:b206744753 "2"^^ . _:b29857 _:b29871 . _:b29856 "Peptides of eight amino acids from TRP-2 were then synthesized using the H2-Kb binding motif described by Rammensee (9, >>10<<). 15 such peptides were identified in the normal reading frame of TRP-2. MC38 murine tumor cells expressing high levels of H2-Kb were incubated with each of these peptides and tested for their ability to stimulate line A T cells." . _:b206744741 . _:b29857 _:b29872 . _:b29857 _:b29873 . _:b29857 _:b29874 . _:b206744752 "2"^^ . . _:b29857 _:b29875 . _:b206744740 . . _:b29857 _:b29876 . _:b29857 _:b29877 . _:b206744755 "2"^^ . _:b206744743 . _:b29852 "Sequences were compared to the Gen-Bank database using the BLAST search engine (>>7<<)." . _:b29875 "As was the case with human gp100 and MART-1, a T cell line with known in vivo antitumor activity was used to screen a tumor cDNA library to identify this antigen (5, >>6<<). In the case of mTRP-2, CTLs with specific activity against the TRP-2181\u2013188 peptide were also effective in treating established B16 tumor, supporting the hypothesis that TRP-2 reactive T cells are at least in part responsible for the in" . _:b206744754 "2"^^ . _:b206744742 . _:b206744729 . . _:b206744775 . _:b206744765 "2"^^ . _:b206744737 . _:b29863 "One group of antigens, characterized by the MAGE (13, 14), BAGE (>>15<<), and GAGE (16) families of proteins, are coded for by normal nonmutated genes, and seem to be expressed by tumor cell, testis, and sometimes placenta, but not other normal tissues." . _:b206744764 "2"^^ . . _:b206744736 . . _:b29861 "One group of antigens, characterized by the MAGE (>>13<<, 14), BAGE (15), and GAGE (16) families of proteins, are coded for by normal nonmutated genes, and seem to be expressed by tumor cell, testis, and sometimes placenta, but not other normal tissues." . _:b29876 . . _:b206744767 "2"^^ . _:b206744739 . . _:b206744758 . _:b206744766 "2"^^ . _:b206744738 . . _:b206744761 "2"^^ . _:b206744749 . _:b206744780 . _:b206744760 "2"^^ . _:b206744748 . . . _:b206744763 "2"^^ . . _:b206744751 . . . _:b206744762 "2"^^ . _:b206744750 . . _:b206744787 . _:b206744773 "2"^^ . _:b206744745 . . . _:b206744772 "2"^^ . _:b206744744 . . _:b206744750 . _:b206744736 . _:b206744775 "2"^^ . _:b206744747 . . . . _:b206744774 "2"^^ . _:b206744746 . _:b206744784 . _:b206744769 "2"^^ . _:b206744757 . . _:b206744812 . . _:b206744768 "2"^^ . . . _:b206744756 . _:b206744771 "2"^^ . _:b206744759 . . _:b206744770 "2"^^ . _:b206744758 . _:b206744781 "2"^^ . _:b206744753 . _:b29853 "results" . _:b206744774 . _:b29874 . _:b206744780 "2"^^ . _:b206744752 . _:b29857 "discussion" . _:b206744783 "2"^^ . _:b206744755 . . _:b206744782 "2"^^ . _:b206744754 . . . _:b206744777 "2"^^ . _:b206744765 . . _:b206744776 "2"^^ . _:b206744731 . _:b206744764 . _:b206744795 . _:b206744779 "2"^^ . _:b206744767 . _:b206744778 "2"^^ . _:b206744766 . . _:b29858 . . _:b29865 "Another major family of antigens represents normal tissue differentiation proteins because they are expressed in melanoma, normal melanocytes, and pigmented retinal cells, and are typified by the proteins tyrosinase (>>2<<, 3), TRP-1 (4), gp100 (6), and MART-1 (5)." . _:b206744789 "2"^^ . _:b206744761 . _:b206744757 . _:b206744788 "2"^^ . . _:b206744760 . _:b206744791 "2"^^ . . _:b206744763 . . . _:b206744790 "2"^^ . _:b206744762 . _:b206744785 "2"^^ . _:b206744805 . _:b206744773 . _:b206744784 "2"^^ . _:b206744772 . . _:b206744787 "2"^^ . _:b206744775 . _:b206744786 "2"^^ . _:b206744774 . . _:b206744742 . _:b206744797 "2"^^ . _:b206744769 . _:b29867 . _:b29858 . . _:b206744796 "2"^^ . _:b206744768 . _:b206744799 "2"^^ . _:b206744771 . _:b29868 "major family of antigens represents normal tissue differentiation proteins because they are expressed in melanoma, normal melanocytes, and pigmented retinal cells, and are typified by the proteins tyrosinase (2, 3), TRP-1 (4), gp100 (>>6<<), and MART-1 (5). Some tumors were also found to express a mutated version of a normal cellular protein which forms a \u201Cforeign\u201D MHC-binding peptide specifically recognized by T cells." . _:b206744798 "2"^^ . _:b206744770 . _:b206744776 . . _:b206744793 "2"^^ . _:b206744781 . _:b206744744 . _:b206744792 "2"^^ . _:b206744780 . _:b206744781 . . _:b206744795 "2"^^ . _:b206744783 . _:b206744794 "2"^^ . _:b206744804 . . _:b206744782 . . _:b206744796 . _:b29869 . _:b206744805 "2"^^ . . _:b206744777 . _:b206744804 "2"^^ . _:b206744776 . _:b206744773 . _:b206744807 "2"^^ . _:b206744779 . . _:b206744765 . . _:b206744806 "2"^^ . . _:b206744778 . . . _:b206744801 "2"^^ . _:b206744789 . _:b29866 . . _:b29863 . _:b206744800 "2"^^ . _:b206744751 . _:b206744788 . _:b29876 "Nevertheless, similar peptides from other immunogenic proteins capable of mimicking TRP-2181\u2013188 may be involved in generating reactivity to this \u201Cself\u201D protein (>>23<<). The peripheral tolerance mechanisms which prevent these precursors from becoming activated in vivo and mediating either B16 rejection or vitiligo are of interest. Overcoming these tolerizing influences may be critical to the future" . _:b29851 "materials and methods" . _:b206744803 "2"^^ . _:b206744791 . _:b206744802 "2"^^ . _:b206744790 . . _:b206744793 . _:b206744813 "2"^^ . _:b206744785 . _:b206744785 . . _:b206744812 "2"^^ . _:b206744784 . _:b206744732 . _:b206744739 . _:b206744815 "2"^^ . _:b206744787 . . _:b29873 . _:b206744814 "2"^^ . _:b206744786 . _:b29871 . _:b206744809 "2"^^ . _:b206744797 . . _:b206744808 "2"^^ . _:b206744796 . _:b206744801 . . _:b206744811 "2"^^ . _:b206744799 . _:b206744802 . _:b206744810 "2"^^ . _:b206744798 . . _:b206744793 . _:b206744753 . _:b29868 . _:b206744792 . _:b206744795 . _:b206744794 . _:b29870 . _:b29877 "Wang et al. have recently demonstrated that human TRP-2 is recognized as a melanoma-associated antigen by a T cell clone from a population of tumor infiltrating lymphocytes which mediated clinical tumor regression (>>24<<). This T cell clone recognized the hTRP-2197\u2013205 peptide of TRP-2 in the context of HLA-A31." . _:b206744805 . . _:b206744816 "2"^^ . _:b206744760 . _:b206744804 . _:b206744764 . _:b206744726 . _:b206744807 . _:b29872 . . _:b29858 . . _:b206744806 . . _:b206744725 . _:b206744816 . . _:b206744741 . _:b29859 . _:b206744810 . _:b206744801 . . _:b206744768 . . _:b206744813 . _:b206744768 . _:b206744769 . _:b206744770 . _:b29872 "The P1A protein of the P815 mastocytoma is analogous to the MAGE family of proteins in that it is encoded by a nonmutated gene which is expressed only in tumor, testis, and placenta (>>18<<\u201321). The Lewis lung carcinoma expresses a mutated form of the connexin 37 protein which is recognized by CD8+ T cells restricted by H2-Kb (22). In the present paper, the first murine tumor\u2013associated antigen recognized by CD8+ T cells" . _:b206744771 . _:b206744800 . _:b206744772 . _:b206744773 . . _:b206744774 . _:b206744775 . _:b206744803 . _:b206744776 . _:b206744777 . _:b206744754 . . _:b206744794 . _:b206744778 . _:b206744779 . _:b206744802 . _:b206744780 . _:b206744803 . _:b206744781 . _:b206744782 . _:b206744783 . _:b206744813 . _:b206744784 . _:b206744785 . _:b206744786 . _:b206744787 . _:b206744812 . _:b206744788 . _:b206744743 . _:b206744789 . _:b206744723 . _:b206744790 . _:b206744791 . _:b206744815 . _:b206744792 . _:b206744793 . _:b206744815 . _:b206744794 . . _:b206744814 . _:b206744795 . _:b206744796 . _:b29855 "Peptides of eight amino acids from TRP-2 were then synthesized using the H2-Kb binding motif described by Rammensee (>>9<<, 10). 15 such peptides were identified in the normal reading frame of TRP-2. MC38 murine tumor cells expressing high levels of H2-Kb were incubated with each of these peptides and tested for their ability to stimulate line A T cells." . . _:b206744788 . _:b206744759 . _:b206744797 . . _:b206744798 . _:b206744799 . _:b206744809 . . _:b206744800 . _:b206744801 . _:b206744802 . _:b29864 "One group of antigens, characterized by the MAGE (13, 14), BAGE (15), and GAGE (>>16<<) families of proteins, are coded for by normal nonmutated genes, and seem to be expressed by tumor cell, testis, and sometimes placenta, but not other normal tissues." . _:b29852 . _:b206744803 . _:b206744808 . _:b206744763 . _:b206744804 . _:b206744805 . _:b206744806 . _:b29853 . _:b206744811 . _:b206744807 . _:b206744808 . _:b206744809 . _:b206744810 . _:b29854 . _:b206744746 . _:b206744810 . _:b206744811 . . . _:b206744812 . _:b206744728 . _:b206744813 . _:b206744814 . _:b29855 . _:b206744749 . _:b206744815 . _:b206744816 . _:b206744806 . . _:b206744792 . . . _:b29875 . _:b29851 . _:b206744747 . _:b29860 . _:b206744816 . _:b29861 . . _:b206744797 . . _:b29856 . _:b29862 . _:b206744748 . _:b29863 . _:b206744722 . _:b29856 . _:b206744723 . _:b206744724 . _:b206744725 . _:b206744726 . _:b206744727 . _:b29857 . _:b206744728 . _:b29865 . _:b206744729 . _:b206744730 . _:b29858 . . _:b206744731 . _:b206744732 . _:b206744733 . _:b206744734 . _:b29859 . _:b206744735 . . _:b206744770 . _:b206744736 . _:b206744737 . _:b206744783 . _:b206744738 . _:b29868 . _:b206744739 . _:b206744791 . _:b206744740 . _:b206744741 . _:b206744742 . _:b29869 . _:b206744743 . _:b206744744 . _:b29855 . _:b206744745 . _:b206744746 . _:b29870 . _:b206744747 . . _:b206744748 . _:b206744749 . . _:b206744750 . _:b29871 . . _:b206744751 . . _:b206744752 . _:b206744753 . _:b206744790 . _:b206744754 . _:b29864 . _:b206744755 . "PMC0" . _:b206744756 . _:b206744757 . _:b206744758 . _:b29867 "Another major family of antigens represents normal tissue differentiation proteins because they are expressed in melanoma, normal melanocytes, and pigmented retinal cells, and are typified by the proteins tyrosinase (2, 3), TRP-1 (>>4<<), gp100 (6), and MART-1 (5). Some tumors were also found to express a mutated version of a normal cellular protein which forms a \u201Cforeign\u201D MHC-binding peptide specifically recognized by T cells." . _:b29865 . _:b206744759 . _:b206744760 . . . _:b206744761 . . _:b29853 _:b29854 . _:b206744762 . _:b29866 . _:b29853 _:b29855 . _:b206744763 . . _:b206744764 . _:b206744765 . _:b206744766 . _:b29867 . . _:b206744767 . _:b29851 _:b29852 . _:b29854 . _:b206744769 . _:b29851 . _:b29876 . _:b206744782 . . _:b29853 . _:b29877 . _:b206744735 . . . _:b29860 "In the last five years, much progress has been made in the molecular identification of tumor cell proteins which are recognized by the cellular immune system in the context of the MHC (4\u20136, 11, >>12<<). Work performed largely with patients with melanoma has identified nearly a dozen tumorassociated antigens which can be divided into several general categories." . _:b206744740 . . _:b206744779 . . _:b206744722 . _:b29872 . . _:b206744734 . _:b206744777 . _:b29873 . . _:b29872 . _:b29874 . _:b29853 _:b29856 . _:b29874 "As was the case with human gp100 and MART-1, a T cell line with known in vivo antitumor activity was used to screen a tumor cDNA library to identify this antigen (>>5<<, 6). In the case of mTRP-2, CTLs with specific activity against the TRP-2181\u2013188 peptide were also effective in treating established B16 tumor, supporting the hypothesis that TRP-2 reactive T cells are at least in part responsible for the" . . _:b206744807 . _:b29875 . _:b206744756 . . _:b29857 . _:b29877 . _:b206744762 . _:b206744725 "5"^^ . _:b206744745 . . _:b206744724 "6"^^ . _:b206744727 "3"^^ .