© The Rockefeller University Press, 0022-1007/2000/3/805/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 5, March 6, 2000 805-812
The Role of Peptides in T Cell Alloreactivity Is Determined by Self–Major Histocompatibility Complex Molecules
Reinhard Obsta,
Nikolai Netuschila,
Karsten Klopfera,
Stefan Stevanovi
a, and
Hans-Georg Rammenseea
a Department of Immunology, Institute for Cell Biology, University of Tübingen, D-72076 Tübingen, Germany
Correspondence to:
Hans-Georg Rammensee, Department of Immunology, Institute for Cell Biology, Eberhard-Karls-University Tübingen, Auf der Morgenstelle 15, D-72076 Tübingen, Germany. Tel:49-7071-298-09-91 Fax:49-7071-29-56-53 E-mail:rammensee{at}uni-tuebingen.de.
Released online: 6 March 2000
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
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