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Original Article |
arammensee{at}uni-tuebingen.de
By analyzing T cell responses against foreign major histocompatibility complex (MHC) molecules loaded with peptide libraries and defined self- and viral peptides, we demonstrate a profound influence of self-MHC molecules on the repertoire of alloreactive T cells: the closer the foreign MHC molecule is related to the T cell's MHC, the higher is the proportion of peptide-specific, alloreactive ("allorestricted") T cells versus T cells recognizing the foreign MHC molecule without regard to the peptide in the groove. Thus, the peptide repertoire of alloreactive T cells must be influenced by self-MHC molecules during positive or negative thymic selection or peripheral survival, much like the repertoire of the self-restricted T cells. In consequence, allorestricted, peptide-specific T cells (that are of interest for clinical applications) are easier to obtain if T cells and target cells express related MHC molecules.
Key Words: peptide library T cell repertoire molecular basis of alloreactivity limiting dilution positive selection
Abbreviations used in this paper: B6, C57BL/6; KbL or DbL, Kb or Db binding peptide library, respectively; Kb(self), mixture of 10 Kb binding self-peptides; TAP, transporter associated with antigen processing; VSV, vesicular stomatitis virus.
© 2000 The Rockefeller University Press
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