HSP70i and other stress proteins have been used in anti-tumor vaccines. This begs the question whether HSP70i plays a unique role in immune... » More

HSP70i and other stress proteins have been used in anti-tumor vaccines. This begs the question whether

HSP70i plays a unique role in immune activation. We vaccinated inducible HSP70i (Hsp70-1) knockout mice

and wild-type animals with optimized TRP-1, a highly immunogenic melanosomal target molecule. We were

unable to induce robust and lasting depigmentation in the Hsp70-1 knockout mice, and in vivo cytolytic

assays revealed a lack of cytotoxic T-lymphocyte activity. Absence of T-cell infiltration to the skin and maintenance

of hair follicle melanocytes were observed. By contrast, depigmentation proceeded without interruption

in mice lacking a tissue-specific constitutive isoform of HSP70 (Hsp70-2) vaccinated with TRP-2. Next, we

demonstrated that HSP70i was necessary and sufficient to accelerate depigmentation in vitiligo-prone Pmel-1

mice, accompanied by lasting phenotypic changes in dendritic cell subpopulations. In summary, these studies

assign a unique function to HSP70i in vitiligo and identify HSP70i as a targetable entity for treatment.

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