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HIV and HCV positive sera are tested with modern epitope mapping methods. Thousands of overlapping peptides
covering the whole sequence of proteins from the HIV and hepatitis C virus have been synthesized by multiple parallel methods
. The B-cell epitopes localized are used as biotinyl peptides for diagnostic purposes
in highly specific ELISA tests and as lipopeptide conjugates for antibody production. The B-cell epitope mapping is supported by conformational mapping and by theoretical methods of conformation prediction. In parallel, a complete T-cell epitope mapping (T-helper and CTL) has been performed.
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1. F. O. Gombert, W. Blecha, M. Tähtinen, A. Ranki, S. Pfeiffer, W. Tröger, R. Braun, N. Müller-Lantzsch,
G. Jung, H. Rübsamen-Waigmann, and K. Krohn (1990).
Antigenic Epitopes of NEF Proteins from Different HIV-1 Strains as Recognized by Sera from Patients with Manifest and
Latent HIV Infection,
Virology 176, 458-466.
2. W. van't Hoff, P. C. Driedijk, M. van den Berg, A. G. Beck-Sickinger, G. Jung, and R.. C. Aalberse (1991).
Epitope Mapping of the
Dermatophagoides pteronyssinus
House Dust Mite Major Allergen Der p II Using Overlapping
Synthetic Peptides,
Mol. Immunol. 28, 1225-1232.
3. N. Zimmermann, A.G. Beck-Sickinger, G. Folkers, S. Krickl, I. Müller, and G. Jung (1991).
Conformational and Epitope Mapping of Herpes simplex Virus Type 1 Thymidine Kinase Using Synthetic Peptide Segments,
Eur. J. Biochem. 200, 519-528.
4. G. Jung and A. G. Beck-Sickinger (1992).
Multiple Peptide Synthesis Methods and Their Applications,
Angew. Chem. 104, 375-391; Angew. Chem. Int.
Ed. Engl. 31, 367-383.
5. K.-H. Wiesmüller, G. Spahn, D. Handtmann, F. Schneider, G. Jung, and C.P. Muller (1992).
Heterogeneity of Linear B Cell Epitopes of the Measles Virus Fusion Protein Reacting with Late Convalescent Sera,
J. Gen. Virol. 73, 2211-2216.
6. M. Tähtinen, F. Gombert, E.-R. Hyytinen, G. Jung, A. Ranki, and K. J. E. Krohn (1992).
Fine Specificity of the B Cell Epitopes Recognized in HIV-1 Nef by Human Sera,
Virology 187, 156-164.
7. H. Siakkou, S. Jahn, N. Kienzle, R. Ulrich, C. Grötzinger, T. Schneider, B. Kohleisen, G. Pauli, R. Spohn,
G. Jung, N. Müller-Lantzsch, and D. H. Krüger (1993).
Fine Mapping of HIV-1 Nef-Epitopes by Monoclonal Antibodies,
Arch. Virol. 128, 81-95.
8. A. G. Beck-Sickinger and G. Jung (1993).
Epitope Mapping: Synthetic Approaches to the Understanding of Molecular Recognition in the Immune System,
Pharmac. Acta Helv. 68, 3-20.
9. V. Blazevic, A. Ranki, S. Mattinen, S.-L. Valle, S. Koskimies, G. Jung, and K.J.E. Krohn (1993).
Helper T-Cell Recognition of HIV-1 Tat Synthetic Peptides,
J. Acquir. Immune Defic. Syndr. 6, 881-890.
10. C.P.Muller, D.Handtmann, N.H.C.Brons, M. Weinmann, K.-H.Wiesmüller, G.Spahn, M. Wiesneth, F. Schneider, and
G. Jung (1993).
Analysis of Antibody Response to the Measles Virus Using Synthetic Peptides of the Fusion Protein. Evidence of
Non-random Pairing of B and T Cell Epitopes,
Virus Res. 30, 271-280.
11. A.G. Beck-Sickinger, H. Rotering, K.-H. Wiesmüller, F. Dorner, and G. Jung (1994).
Mapping of Antigenic and Immunogenic Sites of
Haemophilus influenzae
Outer Membrane Protein P6 with
Synthetic Lipopeptides,
Biol. Chem. Hoppe-Seyler 375, 173-182.
12. J.-P. Borg, H.G. Ihlenfeldt, G. Jung, G. Haas, and M. Pierres (1994).
HIV-1 Reverse Transcriptase Immunodominant CD4
+
T Cell Epitopes: A Peptide-Based Multiparametric
Assessment in Mouse,
Eur. J. Immunol. 24, 1496-1502.
13. C.P. Muller, R. Bünder, H. Mayser, S. Ammon, M. Weinmann, N.H.C. Brons, F. Schneider, G. Jung, and K.-H.
Wiesmüller (1995).
Intramolecular Immunodominance and Intermolecular Selection of H2
d
-Restricted Peptides Define the
Same Immunodominant Region of the Measles Virus Fusion Protein,
Mol. Immunology 32, 37-47.
14. F. Hachida, G. Haas, N. Zimmermann, A. Hosmalin, R. Spohn, G. Jung, A. Samri, P. Debre, and B. Autran (1995)
CTLs from Lymphoid Organs Recognize an Optimal HLA-A2-Restricted and HLA-B52-Restricted Nonapeptide and
Several Epitopes in the C-Terminal Region of HIV-1 Nef,
J. Immunol. 154, 4174-4186.
15. 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.
16. U. Altenschmidt, P. Ricciardi-Castagnoli, M. Modolell, H. Otto, K.-H. Wiesmüller, G. Jung, and
M.M. Simon (1996)
Bone-Marrow Derived Macrophage Lines and Immortalized Cloned Macrophage and Dendritic Cells Support
Priming of
Borrelia burgdorferi
-Specific T-Cell Responses in vitro and/or in vivo,
Immunol. Lett. 50, 41-49.
17. D. Ziegler, P. Fournier, G.A.H. Berbers, H. Steuer, K.-H. Wiesmü:ller, B. Fleckenstein, F. Schneider,
G. Jung, and C.P. Muller (1996)
Protection Against Measles Virus Encephalitis by Monoclonal Antibody Binding to a Cystine Loop Domain of the
H Protein Mimicked by Peptides Which are not Recognized by Maternal Antibodies,
J. Gen. Virol. 77, 2479-2489.
18. M. Lechmann, H.-G.Ihlenfeldt, I. Braunschweiger, G. Giers, G. Jung, B. Matz, D. Kaiser, T. Sauerbruch,
and U. Spengler (1996)
T- and B-Cell Responses to Different Hepatitis C Virus Antigens in Patients with Chronic Hepatitis C
Infection and in Healthy Anti-Hepatitis C Virus-Positive Blood Donors without Viremia,
Hepatology 24, 790-795.
19. G. Haas, U. Plikat, P. Debre, M. Lucchiari, C. Katlama, Y. Dudoit, O. Bonduelle, M. Bauer, H.-G. Ihlenfeldt,
G. Jung, B. Maier, A. Meyerhans, and B. Autran (1996)
Dynamics of Viral Variants in HIV-1 Nef and Specific Cytotoxic T Lymphocytes
in vivo
,
J. Immunol. 157,4212-4221.
20. P. Fournier, W. Ammerlaan, D. Ziegler, C. Giminez, C. Rabourdin-Combe, B. Fleckenstein, K.-H. Wiesmüller,
G. Jung, F. Schneider, and C.P. Muller (1996)
Differential Activation of T Cells by Antibody-Modulated Processing of the Flanking Sequences
of Class II-restricted Peptides,
Int. Immunol. 8, 1441-1451.
21. C.P. Muller, W. Ammerlaan, B. Fleckenstein, S. Krauss, H. Kalbacher, F. Schneider, G. Jung, and
K.-H. Wiesmüller (1996)
Activation of T Cells by the Ragged Tail of MHC Class II-Presented Peptides of the Measles Virus Fusion
Protein,
Int. Immunol. 8, 445-456.
22. P. Fournier, N.H.C. Brons, G.A.H. Berbers, K.-H. Wiesmüller, B. Fleckenstein, H. Steuer, G. Jung,
and C.P. Muller (1997)
Antibodies to a New Linear Site at the Topographic or Functional Interface Between the Hemagglutinin
and Fusion Protein Protect Against Measles Encephalitis,
J. Gen. Virol. 77, 2479-2489.
23. A. Zibert, H. Meisel, W. Kraas, A. Schulz, G. Jung, and M. Roggendorf (1997)
Early Antibody Response Against Hypervariable Region 1 is Associated with Acute Self-Limiting Infections
of Hepatitis C Virus,
Hepatology 25, 1245-1249.
24. A. Zibert, W. Kraas, H. Meisel, G. Jung, and M. Roggendorf (1997)
Epitope Mapping of Antibodies Directed Against Hypervariable Region 1 in Acute Self-Limiting and Chronic
Infections due to Hepatitis C Virus,
J. Virol. 71, 4123-4127.
cojinfo@uni-tuebingen.de(cojinfo@uni-tuebingen.de) - July 23, 1997