PRESENSITIZATION BY SKIN-GRAFTING FROM MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I OR MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II DEFICIENT MICEIDENTIFIES CLASS-I ANTIGENS AS INDUCERS OF ALLOSENSITIZATION

Livers but not hearts are accepted spontaneously without immunosuppres sion when transplanted from B10 (K(b)A(b)E(b)D(b)) to C3H (K(k)A(k)E(k )D(k)) mice. Both organs however, undergo accelerated rejection in C3H recipients presensitized with B10 skin grafts. In this study, we have investigated further the role of functional cell-surface major histoc ompatibility complex (MHC class I or class II molecules in allosensiti zation. Skin from transgenic MHC class I (b2m(mlUnc)bcr;A(b)E(b)) or c lass II (C2D(TM), (KDb)-D-b) gene 'knockout' mice was grafted onto nai ve recipients 2-3 weeks prior to whole organ transplantation. When C3H hosts were presensitized with skin from C2D(TM) (class II deficient) mice, they promptly rejected (within 4 days) subsequently transplanted B10 liver or heart allografts. In contrast, presensitization with ski n from b2m (beta 2-m mutant; class I deficient) mice did not significa ntly affect the survival of either organ graft, Maximal sensitization was established by day 14 after skin grafting and persisted for at lea st 12 weeks. Splenocytes obtained from C3H mice sensitized with skin f rom B10, B6 (K(b)A(b)E(b)D(b)), or C2D(TM) but not from b2m mice exhib ited an H-2(b)-specific cytolytic response when tested in cell-mediate d lymphocytotoxicity assays. Sera from C3H mice sensitized with B10 or b2m skin contained high titres of cytotoxic activity specifically aga inst H-2(b) class I. Taken together, these observations suggest that i n the strain combination studied, MHC class I rather than class II mol ecules play an important role in allosensitization. The results indica te the potential importance of avoiding transplantation of organs into recipients of secondary grafts from donors that share human leucocyte antigen (HLA) class I antigens with the first donor.