PMID- 24183726 OWN - NLM STAT- MEDLINE DCOM- 20140326 LR - 20131125 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 441 IP - 3 DP - 2013 Nov 22 TI - Cytokeratin 8-MHC class I interactions: a potential novel immune escape phenotype by a lymph node metastatic carcinoma cell line. PG - 618-23 LID - S0006-291X(13)01786-5 [pii] LID - 10.1016/j.bbrc.2013.10.105 [doi] AB - Defective human leukocyte antigen (HLA) class I expression in malignant cells facilitates their escape from destruction by CD8(+) cytotoxic T lymphocytes. In this study, a post-translational mechanism of HLA class I abnormality that does not involve defects in the HLA subunits and antigen processing machinery components was identified and characterized. The marked HLA class I downregulation phenotype of a metastatic carcinoma cell line can be readily reversed by trypsin, suggesting a masking effect by serine protease-sensitive HLA class I-interacting factors. Co-immunoprecipitation, combined with LC-tandem mass spectrometry and immunoblotting identified these factors as cytokeratin (CK) 8 and its heterodimeric partners CK18 and CK19. Ectopic CK8/18 or CK8/19 expression in HEK293 cells resulted in surface CK8 expression with an HLA class I downregulation phenotype, while redirecting CK8/18 and CK8/19 to the endoplasmic reticulum (ER) had no such effect. This observation and the failure to constrain CK8/18 and CK8/19 membrane trafficking by an ER-Golgi transport inhibitor suggested an ER-independent route for CK8 access to HLA class I molecules. Monoclonal antibody mapping revealed a potential CK8 blockade of HLA class I-CD8 and -TCR contacts. These findings, along with the emerging role of cell surface CK8 in cancer metastasis, may imply a dual strategy for tumor cell survival in the host. CI - Copyright (c) 2013 Elsevier Inc. All rights reserved. FAU - Wu, Ming-Syue AU - Wu MS AD - Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu, Taiwan. FAU - Li, Chia-Hsuan AU - Li CH FAU - Ruppert, Jan Gustav AU - Ruppert JG FAU - Chang, Chien-Chung AU - Chang CC LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131030 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Antibodies, Monoclonal) RN - 0 (Histocompatibility Antigens Class I) RN - 0 (Keratin-18) RN - 0 (Keratin-19) RN - 0 (Keratin-8) RN - EC 3.4.21.4 (Trypsin) SB - IM MH - Amino Acid Sequence MH - Antibodies, Monoclonal MH - Carcinoma/*secondary MH - Cell Line, Tumor MH - HEK293 Cells MH - Histocompatibility Antigens Class I/*immunology MH - Humans MH - Immunoprecipitation MH - Keratin-18 MH - Keratin-19 MH - Keratin-8/*immunology MH - Lymph Nodes/immunology/pathology MH - Lymphatic Metastasis/*immunology MH - Molecular Sequence Data MH - Protein Multimerization MH - Trypsin/immunology MH - *Tumor Escape OTO - NOTNLM OT - Cytokeratin OT - Human leukocyte antigen OT - Tumor immune escape EDAT- 2013/11/05 06:00 MHDA- 2014/03/29 06:00 CRDT- 2013/11/05 06:00 PHST- 2013/10/02 00:00 [received] PHST- 2013/10/20 00:00 [accepted] PHST- 2013/11/05 06:00 [entrez] PHST- 2013/11/05 06:00 [pubmed] PHST- 2014/03/29 06:00 [medline] AID - S0006-291X(13)01786-5 [pii] AID - 10.1016/j.bbrc.2013.10.105 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2013 Nov 22;441(3):618-23. doi: 10.1016/j.bbrc.2013.10.105. Epub 2013 Oct 30.