Sequence motifs of naturally processed and MHC-bound peptides:  The elucidation of the “immunological code”

Pool sequencing and HPLC-MS allowed for the first time the discovery of sequence motifs of naturally processed peptides, which have been isolated from MHC class I and II molecules. The experimental results have been achieved in cooperation with immunobiologists, in particular with  H.G. Rammensee’s group.

The allele-specific sequence motifs are of fundamental importance for the understanding of the cellular immune response. This knowledge allows the construction of patient-specific novel vaccines such as lipopeptide vaccines and mRNA vaccines with CTL and T-helper responses against tumors, viruses and bacteria. The molecular origin of autoimmune diseases is a further research topic in the context of patient-specific peptide motifs.

O. Rötzschke, K. Falk, K. Deres, H. Schild, M. Noda, J. Metzger, G. Jung, and H.-G.
Rammensee (1990). Isolation and Analysis of Naturally Processed Viral Peptides as Recognized by Cytotoxic T Cells, Nature 348, 252-254.

K . Falk, O. Rötzschke, S. Stevanovic, G. Jung, and H.-G. Rammensee (1991).
Allele-Speciflc Motifs Revealed by Sequencing of Self-Peptides Eluted from MHC-
Nature 351,290-296.

O. Rötzschke, K Falk, S. Stevanovic , B. Grahovac, M. J. Soloski, G. Jung, and H.-G.
Rammensee (1993). Qa-2 Molecules are Peptide Receptors of Higher Stringency than Ordinary Class II Molecules, Nature 361, 642-644.

 K. Falk, O. Rötzschke, B. Grahovac, D. Schendel, S. Stevanovic, V. Gnau, G. Jung,
J.L. Strominger, and H.-G. Rammensee (1993). Allele-Specific Peptide Ligand Motifs of HLA-C Molecules, Proc. Nat. Acad. Sci. 90, 12005-12009.

N. Zimmermann, O. Rötzschke, K. Falk, D. Rognan, G. Folkers, H.-G. Rammensee,
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S. Stevanovic  and G. Jung (1993). Multiple Sequence Analysis: Pool Sequencing of Synthetic and Natural Peptide Libraries, Anal. Biochem. 212, 212-220.

K. Falk, O. Rötzschke, S. Stevanovic, V. Gnau, K. Sparbier, G. Jung, H.-G. Rammen-
see, and P. WaIden (1994). Analysis of a Naturally Occuring MHC-Class I Restricted Viral Epitope, Immunol. 82, 337-342.

G. Malcherek, V. Gnau, S.Stevanovic, H.-G. Rammensee, G. Jung, and A.Melms
(1994). Analysis of Allele-Speciflc Contact Sites of Natural HLA-DR17 Ligands, J. Immu-

G. Malcherek, V. Gnau, G. Jung, H.-G. Rammensee, and A. Melms (1995).
Supermotifs Enable Natural Invariant Chain-Derived Peptides to Interact with
Many Major Histocompatibility Complex-Class II Molecules,
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G. Niedermann, S. Butz, H.-G. Ihlenfeldt, R. Grimm, M. Lucchiari, H. Hoschützky, G.’
Jung, B. Maier, and K. Eichmann (1995). Contribution of Proteasome Mediated Proteolysis to the Hierarchy of Epitopes Presented by MHC Class I, Immunity 2,289-299.

A. Steinle, K. Falk, O. Rötzschke, V. Gnau, S. Stevanovic, G. Jung, D.J. Schendel, and
H.-G. Rammensee (1996). Motif of HLA-B*3503 Peptide Ligands, Immunogenetics 43,105-107.

S. Höpner, K. Dickhaut, M. Hofstätter, H. Krämer, D. Rückerl, J.A. Söderhäll,
S.  Gupta, V. Marin-Esteban, R. Kühne, C. Freund, G. Jung, K. Falk, and O. Rötz-
schke (2006). Small Organic Compounds Enhance Antigen-loading of Class II Major
Histocompatibility Complex Proteins by Targeting the Polymorphic P1
J. Biol. Chem. 281, 38535-38542.

S. Gupta, S. Höpner, B. Rupp, S. Günther, K. Dickhaut, N. Agarwal, C. Cardoso,
R. Kühne, K.-H. Wiesmüller, G. Jung, K. Falk, and O. Rötzschke (2008).
Anchor Side Chains of Short Peptide Fragments Trigger Ligand-Exchange of
Class II MHC Molecules,
PLoS ONE, 3, 1-10.

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