In:
The Journal of Immunology, The American Association of Immunologists, Vol. 178, No. 1_Supplement ( 2007-04-01), p. S168-S168
Abstract:
Direct antigen presentation involves the generation of peptides by proteasomes, ferrying of peptides from cytosol to endoplasmic reticulum and finally, formation and transport of peptide-MHC I complexes. Chaperones hsp90, hsp70, gp96 and TriC have previously been shown to associate with MHC class I epitopes and their precursors. Here, we have treated cells with hsp90 inhibitors Radicicol, 17-AAG or geldanamycin and observe that (i) treatment of cells with such inhibitors leads, in a dose-and time- dependent fashion, to a decrease in the levels of peptide-bound but not total cell surface MHC I; (ii) Radicicol does not affect transport of non-MHC I, control proteins to the cell surface; (iii) Radicicol does not impair MHC I synthesis; and (iv) the reduction in surface MHC I expression caused by Radicicol, is restored by pulsing cells with exogenous peptides. These results indicate an essential role for hsp90 in peptide-transport during endogenous (direct) presentation. During indirect or cross-presentation, antigen presenting cells acquire, process and present exogenous antigen onto the MHC I. Our previous studies (Binder and Srivastava, 2005, Nature Immunology 6, 593) have shown an essential role for HSP-chaperoned peptides in this process. In that study, cell lysates replete with or depleted of one or several HSP-peptide complexes were used to study cross-priming. We have now examined cross-priming by intact cells instead of cell lysates and we observe that hsp90 plays a unique, essential and non-redundant role in cross-priming as well. Data that bear on the mechanism of post-proteasomal transport of peptides, shall be presented.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.178.Supp.93.13
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2007
detail.hit.zdb_id:
1475085-5
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