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Pandya, M.J.* ; Bendz, H. ; Manzenrieder, F.* ; Nößner, E. ; Kessler, H.* ; Buchner, J.* ; Issels, R.D.

Interaction of human heat shock protein 70 with tumor-associated peptides.

Biol. Chem. 390, 304-312 (2009)
Open Access Green as soon as Postprint is submitted to ZB.
Molecular chaperones of the heat shock protein 70 (Hsp70) family play a crucial role in the presentation of exogenous antigenic peptides by antigen-presenting cells (APCs). In a combined biochemical and immunological approach, we characterize the biochemical interaction of tumor-associated peptides with human Hsp70 and show that the strength of this interaction determines the efficacy of immunological cross-presentation of the antigenic sequences by APCs. A fluorescein-labeled cytosolic mammalian Hsc70 binding peptide is shown to interact with human Hsp70 molecules with high affinity (K-d=0.58 mu M at 25 degrees C). Competition experiments demonstrate weaker binding by Hsp70 of antigenic peptides derived from the tumor-associated proteins tyrosinase (K-d=32 mu M) and melanoma antigen recognized by T cells (MART-1) (K-d=2.4 mu M). Adding a peptide sequence (pep70) with high Hsp70 binding affinity (K-d=0.04 mu M) to the tumor-associated peptides enables them to strongly interact with Hsp70. Presentation of tumor-associated peptides by B cells resulting in T cell activation in vitro is enhanced by Hsp70 when the tumor-associated peptides contain the Hsp70 binding sequence. This observation has relevance for vaccine design, as augmented transfer of tumor-associated antigens to APCs is closely linked to the vaccine's efficacy of T cell stimulation.
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Publication type Article: Journal article
Document type Scientific Article
Keywords antigen presentation; antigenic peptide; anti-tumor T cell response; heat shock protein 70; molecular chaperone; peptide binding; heat-shock proteins; molecular chaperone; antigen presentation; binding-specificity; substrate-binding; fluorescein isothiocyanate; transcription factor; complex-formation; dendritic cells; t-lymphocytes
ISSN (print) / ISBN 1431-6730
e-ISSN 1437-4315
Quellenangaben Volume: 390, Issue: 4, Pages: 304-312 Article Number: , Supplement: ,
Publisher de Gruyter
Reviewing status Peer reviewed