Clustering of Major Histocompatibility Complex-Class I Molecules in Healthy and Cancer Colon Cells Revealed from Their Nanomechanical Properties.

Autor:	Moretti M; Single Molecule Imaging by Light Enhanced Spectroscopies Lab, King Abdullah University of Science and Technology, 23955-6900 Thuwal, Jeddah, Kingdom of Saudi Arabia., La Rocca R; Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genova, Italy., Perrone Donnorso M; Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genova, Italy., Torre B; Single Molecule Imaging by Light Enhanced Spectroscopies Lab, King Abdullah University of Science and Technology, 23955-6900 Thuwal, Jeddah, Kingdom of Saudi Arabia., Canale C; Department of Physics, University of Genova, Via Dodecaneso 33, 16146 Genova, Italy., Malerba M; Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genova, Italy., Das G; Department of Physics, Khalifa University, P. O. Box 127788 Abu Dhabi, United Arab Emirates., Sottile R; Katharine Hsu Lab, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, United States., Garofalo C; Department for Experimental and Clinical Medicine, University of Catanzaro, Viale Europa, 88100 Catanzaro, Italy., Achour A; Science for Life Laboratory, Department of Medicine, Solna, Karolinska Institute, and Division of Infectious Diseases, Karolinska University Hospital, 17176 Solna, Stockholm, Sweden., Kärre K; Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Biomedicum Solnavägen 9, 17165 Solna, Stockholm, Sweden., Carbone E; Dipartimento Medicina di Precisione, Università della Campania, via L. De Crecchio, 7, 80138 Naples, Italy., Di Fabrizio E; Department of Applied Physics, Polytechnic University of Turin, Corso Duca degli Abruzzi, 24, 10129 Torino, Italy.
Jazyk:	angličtina
Zdroj:	ACS nano [ACS Nano] 2021 Apr 27; Vol. 15 (4), pp. 7500-7512. Date of Electronic Publication: 2021 Mar 22.
DOI:	10.1021/acsnano.1c00897
Abstrakt:	The activation of the T cell mediated immune response relies on the fine interaction between the T cell receptor on the immune cell and the antigen-presenting major histocompatibility complex (MHC) molecules on the membrane surface of antigen-presenting cells. Both the distribution and quantity of MHC/peptide complexes and their adequate morphological presentation affect the activation of the immune cells. In several types of cancer the immune response is down-regulated due to the low expression of MHC-class I (MHC-I) molecules on the cell's surface, and in addition, the mechanical properties of the membrane seem to play a role. Herein, we investigate the distribution of MHC-I molecules and the related nanoscale mechanical environment on the cell surface of two cell lines derived from colon adenocarcinoma and a healthy epithelial colon reference cell line. Atomic force microscopy (AFM) force spectroscopy analysis using an antibody-tagged pyramidal probe specific for MHC-I molecules and a formula that relates the elasticity of the cell to the energy of adhesion revealed the different population distributions of MHC-I molecules in healthy cells compared to cancer cells. We found that MHC-I molecules are significantly less expressed in cancer cells. Moreover, the local elastic modulus is significantly reduced in cancer cells. We speculate that these results might be related to the proven ability of cancer cells to evade the immune system, not only by reducing MHC-I cell surface expression but also by modifying the local mechanical properties affecting the overall morphology of MHC-I synapse presentation to immune cells.
Databáze:	MEDLINE
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