Effect of invariant chain on major histocompatibility complex class I molecule expression and stability on human breast tumor cell lines
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Invariant chain (Ii) binds to the human leukocyte antigen (HLA) class II molecule and assists it in the process of peptide acquisition. In addition, Ii binds to the HLA class I molecule, although there has been little study of its effects on the HLA class I molecule. In addition to its normal expression on antigen-presenting cells, Ii expression is up regulated in a variety of tumors. By flow cytometric analysis, we found that expression of Ii resulted in an increase in the number of cell surface HLA class I molecules and in the proportion of unstable HLA class I molecules at the surface of breast tumor cell lines. These data suggest that the expression of Ii by tumor cells may quantitatively and qualitatively alter the presentation of antigens on those cells.
KeywordsAntigen presentation Breast cancer Antigens/peptides/epitopes Invariant chain MHC class I molecule
The authors thank Austin Ahles for her assistance with this project. We also thank Dr. Shantaram Joshi, Dr. Kenneth Cowan, Dr. Vinod Labhasetwar, Dr. Michael A. Hollingsworth, Dr. Richard MacDonald, Christopher Connelly, Michelle Hartman, Jaspreet Vasir, Tom Caffrey, Dr. Pankaj Singh, Dr. Peter Cresswell and Dr. Ted Hansen for their assistance with obtaining cell lines, and Dr. Eric Long for the RSV.5neo Vector. We gratefully acknowledge the assistance of the personnel of the University of Nebraska Medical Center Cell Analysis Facility and the Monoclonal Antibody Facility. Core facilities at the University of Nebraska Medical Center receive support from the NIH/NCI Cancer Center Support Grant P30CA036727 (to the Eppley Cancer Center) and the Nebraska Research Initiative. This work was supported by NIH/NIGMS R01 Grant GM057428 and an LB506 Nebraska DHHS Cancer & Smoking Disease Research Grant (to J.C.S.), a Structural Biology and Biophysics Training Program Fellowship from the Department of Education Graduate Assistance in Areas of National Need Program (to H.L.C), NIH/NCI Training Grant T32 CA009476 Fellowship (to L.C.S.), UNMC Graduate Studies Fellowships (to L.C.S. and A.T.), NIH/NRSA Fellowship F32 AI055152 (to C.R.M.), and DOD Breast Cancer Training Program DAMD 17-00-1-0361 Fellowship (to A.J.R.).
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