Figure 1. Hypothesis for antigen presentation and T-cell activation in OLP. Initially, the CD8⁺ T-cell antigen receptor engages a specific foreign antigen (Ag 1) in the context of MHC class I on the basal keratinocyte target cell in OLP [1]. The CD8⁺ T-cell may then seek CD4⁺ T-cell confirmation by expressing the hypothetical "request cytotoxic activity" (RCA) cell surface molecule [2]. The CD4⁺ T-cell expresses the hypothetical "RCA receptor" (RCA R) [4], but only following CD4⁺ T-cell antigen receptor engagement of a related foreign antigen (Ag 2) in the context of MHC class II on the antigen-presenting cell (basal keratinocyte or Langerhans cell in OLP) [3]. Ligation between RCA and RCA R in combination with co-stimulatory signals from the MHC class II⁺ antigen-presenting cell (e.g., CD40, CD80, and IL-12 binding CD154, CD28, and IL-12 R, respectively, on the CD4⁺ T-cell) initiates Th1 differentiation of the CD4⁺ T-cell that then secretes IL-2 and IFN- [5]. Receptors for IL-2 and IFN- are expressed by the CD8⁺ T-cell, but only following (i) specific engagement of the CD8⁺ T-cell antigen receptor in the context of MHC class I and/or (ii) ligation between RCA and RCA R. The CD4⁺ Th1 cytokines (IL-2 and IFN-) are detected by the CD8⁺ T-cell and interpreted as confirmation to proceed with target cell (basal keratinocyte) lysis. Keratinocyte activation by (i) the CD4⁺ or CD8⁺ T-cell following receptor-antigen-MHC trimerization or (ii) exogenous agents such as viral infection, bacterial products, mechanical trauma, systemic drugs, or contact sensitivity up-regulates keratinocyte cytokine and chemokine secretion [6] that promotes lymphocyte extravasation and directs lymphocyte migration into the site of the developing OLP lesion.

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