title: CD91-dependent programming of T-helper cell responses following heat shock protein immunization.
abstract: The immunogenic heat shock proteins (HSPs) gp96, hsp70 and calreticulin (CRT) bind to CD91 on antigen-presenting cells (APCs) for cross-presentation of the HSP-chaperoned peptides. This event leads to priming of T-cell responses. Here we show that CD91 serves as a signalling receptor for these HSPs, allowing for the maturation of APCs, secretion of cytokines and priming of T-helper (Th) cells. Specifically, CD91 is phosphorylated in response to HSPs in a unique pattern and phospho-CD91 triggers signalling cascades to activate nuclear factor-kappa B. Each HSP-CD91 interaction on APCs stimulates a unique cytokine profile, which dictates priming of specific Th cell subsets. Thus, in a transforming growth factor-β tumour microenvironment, immunization with CRT, but not gp96 or hsp70, primes Th17-cell responses in a CD91-dependent manner. These results are important for development of T-cell responses in situ in tumour-bearing hosts and for vaccination against cancer and infectious disease.
authors: Department of Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
authors: Sudesh
authors: S
authors: Pawaria
authors: Robert J
authors: RJ
authors: Binder
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D037282:Calreticulin / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D045142:Cross-Priming / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology* / Q000378:metabolism; D015151:Immunoblotting; D047468:Immunoprecipitation; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism
chemical_list: D037282:Calreticulin; D018840:HSP70 Heat-Shock Proteins; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008562:Membrane Glycoproteins; D034741:RNA, Small Interfering; C053387:endoplasmin