Allergic contact dermatitis is a T-cell-mediated inflammatory skin disease in which interaction between skin keratinocytes and migrating T lymphocytes may play a critical part. In this study, the role of keratinocytes as allergen-/antigen-presenting cells (APCs) leading to activation of T lymphocytes is investigated using a human epidermal cell line A431. It is known that cultured cells do not express human leucocyte antigen (HLA) and hence can be used as APCs independent of HLA profile of both APCs and T cells from human volunteers. This cell line responded to common allergens and irritants by inducing or upregulating the cell-surface expression of HLA-DR, and intercellular adhesion molecule-1 and B7 mRNA transcripts in keratinocytes. In addition, allergen-primed A431 cells also induced allergen-specific proliferation of human T lymphocytes in cocultures. Anti-HLA-DR, interleukin-1alpha (IL-1alpha) antibodies and lysosomotropic agent chloroquine inhibited the proliferation. Allergens also upregulated cytokines IL-1alpha, granulocyte-macrophage colony-stimulating factor, Gro-alpha and IL-12 in keratinocytes. Further, keratinocytes activated by allergens induced polarization of activated T lymphocytes to the Th1 phenotype.