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Pandya, Maya J.; Bendz, Henriette; Manzenrieder, Florian; Noessner, Elfriede; Kessler, Horst; Buchner, Johannes and Issels, Rolf D. (2009): Interaction of human heat shock protein 70 with tumor-associated peptides. In: Biological Chemistry, Vol. 390, No. 4: pp. 304-312 [PDF, 155kB]


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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