Genetic control of contact photosensitivity to tetrachlorosalicylanilide: II. Igh complex controls the sensitivity induced by photohapten-modified spleen cells but not epidermal cells

Abstract

We studied the genetic control of murine contact photosensitivity (CPS) 1 1 Abbreviations used: Ag, antigen; C, complement; CPS, contact photosensitivity; CS, contact sensitivity; CY, cyclophosphamide; DTH, delayed-type hypersensitivity; EC, epidermal cell; ec, epicutaneous; Ig, immunoglobulin; Igh, Ig heavy chain gene complex; Igh-V, variable region of Igh; Igh-C, constant region of Igh; LC, Langerhans cell; Mφ, macrophage; PBS, phosphate-buffered saline; PCI, picryl chloride; photoTCSA-, TCSA-photomodified; SC, spleen cell; sc, subcutaneous; TCSA,3,3′,4′,5-tetrachlorosalicylanilide; TNBS, 2,4,6-trinitrobenzene sulfonic acid; TMA, phenyltrimethylamino; TNP, trinitrophenyl; Ts, suppressor T cells. to 3,3′,4′,5-tetrachlorosalicylanilide (TCSA) that was induced by subcutaneous injection of TCSA-photomodified epidermal cells (photoTCSA-EC) and spleen cells (photoTCSA-SC). With regard to the H-2 locus, sensitization with both types of photohaptenated cells showed the same pattern of CPS responses; H-2 k and H-2 b,d haplotypes were closely associated with low and high responders, respectively. On the other hand, the Igh locus affected the CPS reaction induced by photoTCSA-SC but not-EC; the Igh-1 d allotype was related to low responsiveness, while high responders possessed Igh-1 a,b. Thus, the photoTCSA-SC sensitization was controlled by H-2 and Igh in a codominant manner. The photoTCSA-SC-induced responses of H-2 k but not Igh-1 d mice were enhanced by CY pretreatment, suggesting that the mechanisms of low responsiveness in H-2 k and Igh-l d mice were different. H-2 identity between donors of photoTCSA-EC and recipients was sufficient for effective sensitization, whereas both H-2 and Igh between donors of photoTCSA-SC and recipients should be identical to obtain maximum sensitization. This further confirmed the involvement of the Igh complex in the genetic control of CPS evoked by photoTCSA-SC. B cells as well as macrophages served as an effective presentation template for the photoTCSA-SC sensitization in the high responder Igh-1 a mice, whereas B cells failed in inducing the CPS reaction in the low responder Igh-1 d mice. These results suggest that B cells play an essential role in the Igh control phenomenon seen in the photoTCSA-SC sensitization. The present study demonstrated that CPS induced by photohapten-modified cells are differentially regulated by the H-2 and Igh gene loci depending on the cell type used for sensitization.