ALLO-RESTRICTED AND SELF-RESTRICTED CYTOTOXIC T-LYMPHOCYTES AGAINST APEPTIDE LIBRARY - EVIDENCE FOR A FUNCTIONALLY DIVERSE ALLORESTRICTED T-CELL REPERTOIRE

BALB/c-derived spleen cells were depleted of cytotoxic T lymphocytes ( CTL) recognizing allogeneic (H2(b)) and TAP-negative cells followed by stimulation with the same cells loaded with a synthetic library bindi ng to H2-K-b. The resulting CTL lines were found to differ widely in p eptide specificity and to exhibit an avidity towards the library as th at demonstrated for syngeneic CTL. These results demonstrate that posi tive selection in the context of a certain MHC molecule does not seem to be required for generating high-avidity TCR that are restricted by the same molecule. However, positive selection increases the frequency of such CTL. By raising T cell lines from a repertoire which did not undergo negative selection by the restriction element in question, it becomes possible to produce effective self-peptide/MHC as well as nons elf-peptide/MHC-specific CTL as tools for adoptive tumor immunotherapy .