Optimal T cell activation by melanoma cells depends on a minimal level of antigen transcription

• Published in: The Journal of immunology (1950) Vol. 158; no. 3; pp. 1238 - 1245
• Main Authors: Labarriere, N, Diez, E, Pandolfino, MC, Viret, C, Guilloux, Y, Le Guiner, S, Fonteneau, JF, Dreno, B, Jotereau, F
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.02.1997; Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists
• Subjects: Adaptive immunology; Antigens, Neoplasm - immunology; Antigens, Surface - metabolism; Cancer; CD58 Antigens - metabolism; Gene Expression Regulation, Neoplastic; HLA-A2 Antigen - metabolism; Humans; Immunology; Immunotherapy; Intercellular Adhesion Molecule-1 - metabolism; Interleukin-2 - biosynthesis; Life Sciences; Lymphocyte Activation; Melanoma - genetics; Melanoma - immunology; RNA, Messenger - genetics; RNA, Neoplasm - genetics; T-Lymphocytes - immunology; Transcription, Genetic; Tumor Cells, Cultured
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.158.3.1238

We reported previously that a large fraction of melanoma cell lines induced a suboptimal activation of specific CTL clones, characterized by good tumor cell lysis but no detectable IL-2 production. Using synthetic peptides, we demonstrated recently that this was due to expression of subthreshold levels of appropriate MHC-peptide complexes. We measure here by semiquantitative reverse transcription-PCR the expression of two melanoma Ag (NA17-A and Melan-A/MART-1) mRNAs in 13 melanoma cell lines and analyze the responses to these cell lines of specific HLA-A2-restricted CTL clones. In line with the idea that the density of MHC-antigenic peptide complexes on melanoma cells is a direct function of the Ag's mRNA level, we found that CTL lysis was grossly proportional to this level. We also established that a minimal level of transcription is required for melanoma cells to induce IL-2 secretion. Interestingly, all cell lines that expressed the Ag above this minimal level, either spontaneously or after gene transfection, stimulated the secretion by tumor-infiltrating lymphocyte of IL-2 amounts proportional to Ag expression unless they exhibited a defective expression of intracellular adhesion molecule-1 or LFA-3 molecules or a low expression of the restricting HLA element. These results indicate that optimal activation and therefore, doubtless, full functionality of melanoma-specific CTL clones critically depend on the mRNA level of the Ag in tumor cells and also on a minimal expression of the HLA restriction element, intracellular adhesion molecule-1, and LFA-3. These data provide a rationale for a better selection of patients to be included in Ag-specific immunization protocols.