Cytotoxic T lymphocytes recognize tumor antigens of a murine colonic carcinoma by using different T-cell receptors.
To see whether different antigens expressed by the same tumor are recognized by distinct T-cell receptors (TCR), we used cytotoxic T-lymphocyte (CTL) lines known to lyse in vitro the syngeneic BALB/c adenocarcinoma C-26. Four of these CD3+ CD8+ lines showed 4 different patterns of lysis on a panel of MHC-class-I-compatible targets. The activity was H-2d-restricted and could be blocked by anti-CD3 and anti-TCR-alpha/beta monoclonal antibodies (MAbs). The CTL lines were also effective, although to a different extent, in adoptive immunotherapy of mice bearing lung metastases. Phenotypic analysis revealed in all the lines a high frequency of cells positive for CD45, asialo GM1 (ASGM1), lymphocyte-function-associated antigen-1 (LFA-1), intercellular adhesion molecule-1 (ICAM-1) and CD44, but negligible expression of L-selectin (LAM-1) and very late antigen-4 (VLA-4); 2 lines expressed the vitronectin-receptor (VN-R). Analysis of TCR V beta-chains used by the 4 lines showed selective presence of V beta 6, V beta 8.2, V beta 8.3 and of V beta 13 chains. MAbs directed to these V beta chains blocked their lytic activity in vitro. V alpha-chain transcripts of the lines were identified by polymerase chain reaction (PCR) as V alpha ITT11 and V alpha 52 in 2 lines, while one could not be identified. Analysis of V beta s in mixed lymphocyte-tumor-cell cultures (MLTC) of T cells deriving from tumor-infiltrating lymphocytes (TIL) or from spleen of C-26 tumor-bearing or immune animals indicated that the TCR of the CTL lines were representatives of the TCR repertoire recognizing C-26 tumor, since their V beta s were shown to be selectively expanded in MLTC.
Rodolfo
M
M
Division of Experimental Oncology D, Istituto Nazionale Tumori, Milan, Italy.
Castelli
C
C
Bassi
C
C
Accornero
P
P
Sensi
M
M
Parmiani
G
G
D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D002277:Carcinoma / Q000276:immunology*; D002460:Cell Line; D003110:Colonic Neoplasms / Q000276:immunology*; D005260:Female; D016219:Immunotherapy, Adoptive; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008285:Major Histocompatibility Complex / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000951:Antigens, Neoplasm; D011948:Receptors, Antigen, T-Cell