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Original Article

Reinhard Obst^a, Nikolai Netuschil^a, Karsten Klopfer^a, Stefan Stevanovi^a, and Hans-Georg Rammensee^a

^a Department of Immunology, Institute for Cell Biology, University of Tübingen, D-72076 Tübingen, Germany
Department of Immunology, Institute for Cell Biology, Eberhard-Karls-University Tübingen, Auf der Morgenstelle 15, D-72076 Tübingen, Germany.49-7071-29-56-5349-7071-298-09-91

rammensee{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; K^bL or D^bL, K^b or D^b binding peptide library, respectively; K^b_(self), mixture of 10 K^b binding self-peptides; TAP, transporter associated with antigen processing; VSV, vesicular stomatitis virus.

© 2000 The Rockefeller University Press

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