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
S. Qian et al., 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, Immunology, 85(1), 1995, pp. 82-87
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.