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Graft-versus-host disease (GVHD) may develop after allogeneic bone marrow transplantation (BMT) between donors and recipients incompatible for minor histocompatibility antigens (mHAg). Here, we examined the possible relationship between tissue-specific distribution of dominant mHAg peptides and specific organ destruction caused by GVHD. In the B6 anti-Balb/b (H-2b) strain combination, a GVHD developed against Balb/b mHAgs. Despite the high number of incompatible mHAgs between these two strains, both cytotoxic T lymphocyte (CTL) response and GVHD could be attributed to a limited number of dominant mHAgs. We studied CTL-defined expression of dominant mHAgs in normal tissues and their GVHD-related modifications. mHAg peptides were prepared by acid elution and reversed-phase high pressure liquid chromatography fractionation from the spleen, liver, gut and skin as GVHD target tissues and from the heart and kidney as control tissues. Peptidic fractions extracted from normal and GVHD tissues were incubated with RMA-S targets and analysed using bulk B6 anti-Balb/b CTL. In each tissue several fractions were recognized with a given pattern of mHAg expression. GVHD induced qualitative and quantitative changes in antigenic peptide expression. Modifications in mHAg presentation during GVHD concerned preferentially GVHD target organs as opposed to non-GVHD target organs. In addition, when immunizing tissues were derived from GVHD mice instead of normal mice, the profile of CTL recognition was different. In conclusion, these data indicate that broad differences could exist in peptide presentation between various normal and GVHD-target organs.