From combinatorial libraries to MHC ligand motifs, T-cell superagonists and antagonists.

Complete experimental data sets of HLA-ligand motifs and T-cell recognition patterns can be derived from combinatorial peptide libraries. These data provide the exact molecular basis for a fast development of synthetic vaccines, T-cell superagonists and non-peptide antagonists. Patient-specific peptides, peptidomimetics and vaccines of highest reactivity can be derived directly from the data sets via our prediction programme EPIPREDICT. The resulting lead structures may be developed into valuable diagnostics and therapeutic tools for the treatment of viral infections, autoimmune diseases and tumors. As one example, antibody and T cell recognition in the intestinal auto-immune disease, coeliac disease was investigated in more detail concerning the deamidation of gamma-gliadin peptides by tissue transglutaminase 9tTG) leading to autoreactive peptides specific for HLA-DQA1*0501, DQB1*0201.

[1]  F. Koning,et al.  Increased HLA-DQ2-affinity of a synthetic gliadin peptide by acid-induced deamidation of glutamine residues. , 1998, Bioorganic & medicinal chemistry letters.

[2]  K. Wiesmüller,et al.  Novel low-molecular-weight synthetic vaccine against foot-and-mouth disease containing a potent B-cell and macrophage activator. , 1989, Vaccine.

[3]  W. Bessler,et al.  Solid phase peptide synthesis of lipopeptide vaccines eliciting epitope-specific B-, T-helper and T-killer cell response. , 2009, International journal of peptide and protein research.

[4]  G. Jung,et al.  Cutting edge: N-hydroxy peptides: a new class of TCR antagonists. , 1999, Journal of immunology.

[5]  H. Rammensee,et al.  In vivo priming of virus-specific cytotoxic T lymphocytes with synthetic lipopeptide vaccine , 1989, Nature.

[6]  Günther Jung,et al.  Combinatorial chemistry : synthesis, analysis, screening , 1999 .

[7]  J. Strominger,et al.  Conformational variants of class II MHC/peptide complexes induced by N- and C-terminal extensions of minimal peptide epitopes. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[8]  K. Wiesmüller,et al.  Peptide Libraries in T‐Cell‐Mediated Immune Response , 1999 .

[9]  Gnther Jung,et al.  Combinatorial Peptide and Nonpeptide Libraries , 1996 .

[10]  L. Sollid Molecular basis of celiac disease. , 2000, Annual review of immunology.

[11]  K. Wiesmüller,et al.  Quantitative analysis of peptide-MHC class II interaction. , 1999, Seminars in immunology.