Helmholtz Gemeinschaft


Chaperone protein HSC70 regulates intercellular transfer of Y chromosome antigen DBY.

Item Type:Article
Title:Chaperone protein HSC70 regulates intercellular transfer of Y chromosome antigen DBY.
Creators Name:Kretschmann, S. and Herda, S. and Bruns, H. and Russ, J. and van der Meijden, E.D. and Schlötzer-Schrehardt, U. and Griffioen, M. and Na, I.K. and Mackensen, A. and Kremer, A.N.
Abstract:Recent studies have demonstrated that CD4+ T cells can efficiently reject MHC-II-negative tumors. This requires indirect presentation of tumor-associated antigens on surrounding antigen-presenting cells. We hypothesized that intercellular transfer of proteins is not the sole consequence of cell death-mediated protein release, but depends on heat-shock cognate protein 70 (HSC70) and its KFERQ-like binding motif on substrate proteins. Using human Y chromosome antigen DBY, we showed that mutation of one of its 2 putative binding motifs markedly diminished T cell activation after indirect presentation and reduced protein-protein interaction with HSC70. Intercellular antigen transfer was shown to be independent of cell-cell contact, but relied on engulfment within secreted microvesicles. In vivo, alterations of the homologous KFERQ-like motif in murine DBY hampered tumor rejection, T cell activation, and migration into the tumor and substantially impaired survival. Collectively, we show that intercellular antigen transfer of DBY is tightly regulated via binding to HSC70 and that this mechanism influences recognition and rejection of MHC-II-negative tumors in vivo.
Keywords:Amino Acid Motifs, DEAD-box RNA Helicases, HSC70 Heat-Shock Proteins, HeLa Cells, Histocompatibility Antigens Class II, Lymphocyte Activation, MCF-7 Cells, Minor Histocompatibility Antigens, Neoplasm Proteins, Neoplasms, Protein Transport, Secretory Vesicles, T-Lymphocytes, Animals, Mice
Source:Journal of Clinical Investigation
Publisher:American Society for Clinical Investigation
Page Range:2952-2963
Date:1 July 2019
Official Publication:https://doi.org/10.1172/JCI123105
External Fulltext:View full text on PubMed Central
PubMed:View item in PubMed

Repository Staff Only: item control page

Open Access
MDC Library