We tested for antigen recognition and T cell receptor (TCR)–ligand binding 12 peptide derivative variants on seven H-2Kd–restricted cytotoxic T lymphocytes (CTL) clones specific for a bifunctional photoreactive derivative of the Plasmodium berghei circumsporozoite peptide 252– 260 (SYIPSAEKI). The derivative contained iodo-4-azidosalicylic acid in place of PbCS S-252 and 4-azidobenzoic acid on PbCS K-259. Selective photoactivation of the N-terminal photoreactive group allowed crosslinking to Kd molecules and photoactivation of the orthogonal group to TCR. TCR photoaffinity labeling with covalent Kd–peptide derivative complexes allowed direct assessment of TCR–ligand binding on living CTL. In most cases (over 80%) cytotoxicity (chromium release) and TCR–ligand binding differed by less than fivefold. The exceptions included (a) partial TCR agonists (8 cases), for which antigen recognition was fivetenfold less efficient than TCR–ligand binding, (b) TCR antagonists (2 cases), which were not recognized and capable of inhibiting recognition of the wild-type conjugate, (c) heteroclitic agonists (2 cases), for which antigen recognition was more efficient than TCR–ligand binding, and (d) one partial TCR agonist, which activated only Fas (CD95), but not perforin/granzymemediated cytotoxicity. There was no correlation between these divergences and the avidity of TCR–ligand binding, indicating that other factors than binding avidity determine the nature of the CTL response. An unexpected and novel finding was that CD8-dependent clones clearly incline more to TCR antagonism than CD8-independent ones. As there was no correlation between CD8 dependence and the avidity of TCR–ligand binding, the possibility is suggested that CD8 plays a critical role in aberrant CTL function.
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17 February 1997
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February 17 1997
Effects of Epitope Modification on T Cell Receptor–Ligand Binding and Antigen Recognition by Seven H-2Kd–restricted Cytotoxic T Lymphocyte Clones Specific for a Photoreactive Peptide Derivative
Benedikt M. Kessler,
Benedikt M. Kessler
From the Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, 1066 Epalinges, Switzerland
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Paolo Bassanini,
Paolo Bassanini
From the Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, 1066 Epalinges, Switzerland
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Jean-Charles Cerottini,
Jean-Charles Cerottini
From the Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, 1066 Epalinges, Switzerland
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Immanuel F. Luescher
Immanuel F. Luescher
From the Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, 1066 Epalinges, Switzerland
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Benedikt M. Kessler
From the Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, 1066 Epalinges, Switzerland
Paolo Bassanini
From the Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, 1066 Epalinges, Switzerland
Jean-Charles Cerottini
From the Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, 1066 Epalinges, Switzerland
Immanuel F. Luescher
From the Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, 1066 Epalinges, Switzerland
Address correspondence to Immanuel F. Luescher, Ludwig Institute for Cancer Research, Chemin des Boveresses 155, CH-1066 Epalinges, Switzerland.
1Abbreviations used in this paper: ABA, 4-azidobenzoic acid; ASA, azidosalicylic; IASA, iodo-4-azidosalicylic acid.
Received:
September 26 1996
Revision Received:
December 02 1996
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1997
J Exp Med (1997) 185 (4): 629–640.
Article history
Received:
September 26 1996
Revision Received:
December 02 1996
Citation
Benedikt M. Kessler, Paolo Bassanini, Jean-Charles Cerottini, Immanuel F. Luescher; Effects of Epitope Modification on T Cell Receptor–Ligand Binding and Antigen Recognition by Seven H-2Kd–restricted Cytotoxic T Lymphocyte Clones Specific for a Photoreactive Peptide Derivative. J Exp Med 17 February 1997; 185 (4): 629–640. doi: https://doi.org/10.1084/jem.185.4.629
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