Currently, there are considerable efforts to standardize methods for accurate assessment of properties and safety aspects of nanomaterial. However, immunomodulation effects upon skin exposure to nanomaterial have been negligibly explored.To investigate the immunotoxicity of single-wall carbon nanotubes, titanium dioxide and fullerene using the current mechanistic understanding of skin sensitization by applying the concept of adverse outcome pathway (AOP).Investigation of nanomaterials ability to interact with skin proteins using micro-direct peptide reactivity assay (mDPRA); the expression of CD86 cell surface marker using U937 cell activation Test (OECD No 442E/2018); and the effects of nanomaterials on modulating inflammatory response through inflammatory cytokine release by U937 cells.The nanomaterials easily internalized into keratinocytes cells, interacted with skin proteins like and triggered activation of U937 cells by increasing CD86 expression and modulating inflammatory cytokine production. Consequently, these nanomaterials were classified as skin sensitizers in vitro.Our study suggests the potential immunotoxicity of nanomaterials and highlights the importance of studying the immunotoxicity and skin sensitization potential of nanomaterials to anticipate possible human health risks using standardized mechanistic non-animal methods with high predictive accuracy. Therefore, it contributes towards the applicability of existent OECD TG for accurate assessment of nanomaterial skin sensitization potential. This article is protected by copyright. All rights reserved.