CD91-dependent programming of T-helper cell responses following heat shock protein immunization

Sudesh Pawaria and Robert J. Binder ()
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Sudesh Pawaria: University of Pittsburgh
Robert J. Binder: University of Pittsburgh

Nature Communications, 2011, vol. 2, issue 1, 1-11

Abstract: 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.

Date: 2011
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:2:y:2011:i:1:d:10.1038_ncomms1524

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DOI: 10.1038/ncomms1524

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