MECHANISMS OF INDIRECT ALLORECOGNITION - CHARACTERIZATION OF MHC CLASS-II ALLOPEPTIDE-SPECIFIC T-HELPER CELL CLONES FROM ANIMALS UNDERGOINGACUTE ALLOGRAFT-REJECTION

Background. Recent evidence indicates that T cells primed via the indi rect pathway of allorecognition play an important role in allograft re jection, although the effector mechanisms remain unknown. The purpose of this study was to characterize and study the in vivo function of se lf-restricted MHC allopeptide-specific T-cell clones generated from an imals undergoing allograft rejection. Methods and Results. We generate d self-restricted class II MRC allopeptide-specific T-cell clones from the spleen and kidney of Lewis (LEW; RT1(I)) rats undergoing acute re jection of MBC-incompatible Wistar Furth (WF; RT1(u)) renal allografts , RT1.D-u beta 20-44 peptide-specific CD4(+) T helper 1 clones from th e spleen and kidney of rejecting animals expressed a restricted T cell . receptor (TCR) V beta repertoire: V beta 4, 8.2, or 9. In comparison , clones generated from RT1.D-u beta 20-44 immunized LEW rats all expr essed TCR V beta 9, The amino acid sequence of RT1.D-I (LEW) and RT1.D -u (WF) residues 20-44 differ only at positions 30 and 38. T-cell clon es expressing TCR V beta 9 preferentially proliferated to the peptide fragment RT1.D-u beta 20-33. T-cell clones expressing TCR V beta 4 pro liferated weakly to peptide fragments RT1.D-u beta 20-33 and 31-44, wh ereas those expressing TCR beta P8.2 proliferated preferentially to th e peptide fragment 31-44, Adoptive transfer of T-cell clones expressin g TCR V beta 9 or V beta 8.2, but not V beta 4, to naive LEW animals e licited significant delayed-type hypersensitivity responses after chal lenge with the RT1.D-u beta 20-44 peptide or allogeneic WF (RT1(u)) sp lenocytes, Conclusion. This is the first report on the cellular, molec ular, and functional characterization of self-restricted MHC allopepti de-specific T-cell clones from animals undergoing acute rejection. Our data provide support for a biologically significant role of indirect allorecognition in allograft rejection.