Cell-mediated cytotoxicity to nonmajor histocompatibility complex alloantigens on mouse epidermal cells. V. Contribution of bone marrow-derived cells to Epa-1 antigen expression.

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Epa-1 is a non-H-2 alloantigen preferentially expressed on mouse epidermal cells (ECs) as opposed to lymphoid cells. Immunization in vivo (priming) of Epa-1- C3H/He mice with ECs from the Epa-1+, H-2-compatible CBA strain, followed by boosting host spleen cells (SCs) in mixed leukocyte-EC reactions in vitro, results in the generation of potent cytotoxic T lymphocytes (CTLs) that readily lyse CBA ECs as opposed to SCs in H-2-restricted fashion in short-term chromium release assays. To determine the importance of bone marrow (BM)-derived cells in the epidermis (Langerhans cells) for Epa-1 expression, reciprocal radiation chimeras were produced with the C3H (Epa-1-) and CBA (Epa-1+) strains. After allowing ample time (4 months) for the replacement of host by donor-type Langerhans cells, ECs from the chimeras and from intact C3H and CBA mice, as well as from syngeneically reconstituted radiation controls, were compared for their ability to prime, boost, and serve as targets for anti-Epa-1-CTLs. The results confirm that Epa-1 is expressed mainly by keratinocytes and that the presence of Epa-1+ BM-de-rived cells, presumably Langerhans cells, is not required for the expression of Epa-1 by the bulk of epidermal cells (i.e., keratinocytes), although the BM-derived cells also express Epa-1 in both immunogenic and target cell determinant form. Paradoxically, although Epa-1 is not expressed as a target cell determinant on SCs, it is expressed in immunogenic form because CBA SCs can either prime for or boost the generation of C3H anti-Epa-1 CTLs when combined with CBA EC boosting or priming, respectively. The results of priming and boosting assays using SCs from radiation chimeras and controls indicate that BM-derived and non-BM-derived cells (stromal or reticular cells) in the spleen may express Epa-1 in immunogenic form at comparable levels.