Abstract
We have isolated from tumor-infiltrating lymphocytes (TIL) and PBL of a lung carcinoma patient several tumor-specific T cell clones displaying similar peptide-MHC tetramer staining and expressing a unique TCR. Although these clones elicited identical functional avidity and similar cytolytic potential, only T cell clones derived from TIL efficiently lysed autologous tumor cells. Interestingly, all of these clones expressed the same T cell surface markers except for the TCR inhibitory molecule CD5, which was expressed at much lower levels in TIL than in PBL. Video-imaging recordings demonstrated that, although both T cell clones could form stable conjugates with tumor cells, the Ca(2+) response occurred in TIL clones only. Significantly, analysis of a panel of circulating clones indicated that antitumor cytolytic activity was inversely proportional to CD5 expression levels. Importantly, CD5 levels in TIL appeared to parallel the signaling intensity of the TCR/peptide-MHC interaction. Thus, in situ regulation of CD5 expression may be a strategy used by CTL to adapt their sensitivity to intratumoral peptide-MHC levels.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptation, Physiological / immunology
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CD5 Antigens / biosynthesis
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Carcinoma, Non-Small-Cell Lung / immunology
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Carcinoma, Non-Small-Cell Lung / pathology
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Carcinoma, Non-Small-Cell Lung / prevention & control
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Cell Communication / immunology*
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Cell Line, Tumor
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Clone Cells
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Cytotoxicity, Immunologic / immunology*
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Histocompatibility Antigens Class I / biosynthesis
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Histocompatibility Antigens Class I / metabolism*
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Histocompatibility Antigens Class I / physiology
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Humans
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Immunotherapy, Adoptive / methods
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Leukocytes, Mononuclear / immunology
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Leukocytes, Mononuclear / metabolism
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Lung Neoplasms / immunology
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Lung Neoplasms / pathology
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Lung Neoplasms / prevention & control
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Lymphocytes, Tumor-Infiltrating / immunology*
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Lymphocytes, Tumor-Infiltrating / metabolism*
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Lymphocytes, Tumor-Infiltrating / pathology
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Peptide Fragments / biosynthesis
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Peptide Fragments / metabolism*
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Peptide Fragments / physiology
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Receptors, Antigen, T-Cell, alpha-beta / biosynthesis
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Receptors, Antigen, T-Cell, alpha-beta / physiology
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Signal Transduction / immunology
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Staining and Labeling
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / metabolism*
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T-Lymphocyte Subsets / pathology
Substances
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CD5 Antigens
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Histocompatibility Antigens Class I
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Peptide Fragments
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Receptors, Antigen, T-Cell, alpha-beta
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T cell receptor Vbeta8