The role of peptides in T cell alloreactivity is determined by self-major histocompatibility complex molecules.
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.
Obst
R
R
Department of Immunology, Institute for Cell Biology, University of Tübingen, D-72076 Tübingen, Germany. obst@joslin.harvard.edu
Netuschil
N
N
Klopfer
K
K
Stevanović
S
S
Rammensee
H G
HG
D000818:Animals; D002460:Cell Line; D005805:Genes, MHC Class I / Q000276:immunology*; D014644:Genetic Variation; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000276:immunology*; D019151:Peptide Library; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology
D006183:H-2 Antigens; D009842:Oligopeptides; D019151:Peptide Library