User:Marios F. Sardis: Difference between revisions
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In 1967, a puzzling observation was made by Calne and his laboratory team, during liver transplantation experiments on pigs. One animal survived for months, after receiving an allograft, without any immunosupression. Later, it was found that the soluble factors, which were secreted by the liver allograft and were responsible for the development of tolerance to the recipient animal, were soluble MHC | In 1967, a puzzling observation was made by Calne and his laboratory team, during liver transplantation experiments on pigs. One animal survived for months, after receiving an allograft, without any immunosupression. Later, it was found that the soluble factors, which were secreted by the liver allograft and were responsible for the development of tolerance to the recipient animal, were soluble MHC molecules1,2. From this point, many laboratories around the world entered the quest, for the elucidation of the immunoregulatory effects of the various soluble forms of MHC molecules. Today, it is widely accepted that body fluids, isolated from healthy individuals contain various amounts of soluble MHC molecules1,3,4,5,6. Deviations from the concentration of these molecules in the body fluids of healthy individuals, have been recorded in numerous pathological conditions, such as viral encephalitis5, rheumatoid arthritis7,8,9, pathologic pregnancies10, asthma11 and AIDS5. These results do not clarify whether soluble MHC molecules have a special role in the immune responses, during the course of these diseases. Additional research has confirmed that soluble forms of MHC molecules can have various immunomodulating effects, such as induction of apoptosis of CD4+ T cells12; activation of CD8+ T cells13 and down-regulation of NK activity13. Soluble dimeric MHC class II molecules built on Fcg2a scaffold can cause activation of T cells and switching towards a TH2 response17. According to another report, soluble dimeric IEk molecules can act as potent activators for T cells, especially in the presence of the CD4 coreceptor18. | ||
The main focus of my undergraduate research project was the isolation of soluble MHC molecules and thecollection of data about their biological function. We have collected protein solutions that have been isolated from the serum of male and pregnant Balb/c mice, which show anti-I-Ad activity in ELISA, antibody binding inhibition and Western blot assays. After the isolation process was complete, I proceeded with functional assays in order to gather information about the biological role of these molecules. When spleen cells from syngeneic mice were treated with the protein solutions, we had isolated, a significant increase in the incorporation of radioactivity was recorded. However, in some assays, allogeneic spleen cells (C3H/HeN) responded also positively to the soluble molecules we had isolated. Spleen cells that were treated with Concanavalin A and soluble MHC molecules increased the incorporation of radioactivity in an additive manner. Furthermore, during one way, Mixed Lymphocyte Reactions when Balb/c spleen cells that responded to inactivated with mitomycin C3H/HeN spleen cells, were treated with solution of soluble MHC II molecules, their responses were significantly boosted. | The main focus of my undergraduate research project was the isolation of soluble MHC molecules and thecollection of data about their biological function. We have collected protein solutions that have been isolated from the serum of male and pregnant Balb/c mice, which show anti-I-Ad activity in ELISA, antibody binding inhibition and Western blot assays. After the isolation process was complete, I proceeded with functional assays in order to gather information about the biological role of these molecules. When spleen cells from syngeneic mice were treated with the protein solutions, we had isolated, a significant increase in the incorporation of radioactivity was recorded. However, in some assays, allogeneic spleen cells (C3H/HeN) responded also positively to the soluble molecules we had isolated. Spleen cells that were treated with Concanavalin A and soluble MHC molecules increased the incorporation of radioactivity in an additive manner. Furthermore, during one way, Mixed Lymphocyte Reactions when Balb/c spleen cells that responded to inactivated with mitomycin C3H/HeN spleen cells, were treated with solution of soluble MHC II molecules, their responses were significantly boosted. | ||
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[1]van Rood JJ, van Leeuwen A, van Santen MCT: Anti-HL-A2 inhibitor in normal human serum. Nature (1970) Vol. 226(5243):366<br/> | |||
[2] Jon J. van Rood and Aad van Leeuwen, Soluble HLA Antigens: How It All Started, Human Immunology (1999) Vol. 60:412–413<br/> | [2] Jon J. van Rood and Aad van Leeuwen, Soluble HLA Antigens: How It All Started, Human Immunology (1999) Vol. 60:412–413<br/> | ||
[3]Francesco Puppo Francesco Indiveri, Marco Scudeletti and Soldano Femme, ., Soluble HLA | [3]Francesco Puppo Francesco Indiveri, Marco Scudeletti and Soldano Femme, ., Soluble HLA | ||
Revision as of 08:19, 1 September 2006
Contact info
Sardis Marios Frantzeskos
Department of Biology
University of Crete, Greece
e-mail: hartigan.sc@gmail.com
Education
2002-2006 B.Sc. in Biology (Molecular Biology and Biotechnology), University of Crete.
2001-2002 Certificate of Higher Education, University of Cardiff, Wales, U.K.
Awards
2003-2004 Award granted from the National Institute of Studentships of Greece (IKY) for excellent academic performance.
2003-2004 Studentship granted from the National Institute of Studentships of Greece (IKY) for top academic performance of the year.
Research experience
In 1967, a puzzling observation was made by Calne and his laboratory team, during liver transplantation experiments on pigs. One animal survived for months, after receiving an allograft, without any immunosupression. Later, it was found that the soluble factors, which were secreted by the liver allograft and were responsible for the development of tolerance to the recipient animal, were soluble MHC molecules1,2. From this point, many laboratories around the world entered the quest, for the elucidation of the immunoregulatory effects of the various soluble forms of MHC molecules. Today, it is widely accepted that body fluids, isolated from healthy individuals contain various amounts of soluble MHC molecules1,3,4,5,6. Deviations from the concentration of these molecules in the body fluids of healthy individuals, have been recorded in numerous pathological conditions, such as viral encephalitis5, rheumatoid arthritis7,8,9, pathologic pregnancies10, asthma11 and AIDS5. These results do not clarify whether soluble MHC molecules have a special role in the immune responses, during the course of these diseases. Additional research has confirmed that soluble forms of MHC molecules can have various immunomodulating effects, such as induction of apoptosis of CD4+ T cells12; activation of CD8+ T cells13 and down-regulation of NK activity13. Soluble dimeric MHC class II molecules built on Fcg2a scaffold can cause activation of T cells and switching towards a TH2 response17. According to another report, soluble dimeric IEk molecules can act as potent activators for T cells, especially in the presence of the CD4 coreceptor18. The main focus of my undergraduate research project was the isolation of soluble MHC molecules and thecollection of data about their biological function. We have collected protein solutions that have been isolated from the serum of male and pregnant Balb/c mice, which show anti-I-Ad activity in ELISA, antibody binding inhibition and Western blot assays. After the isolation process was complete, I proceeded with functional assays in order to gather information about the biological role of these molecules. When spleen cells from syngeneic mice were treated with the protein solutions, we had isolated, a significant increase in the incorporation of radioactivity was recorded. However, in some assays, allogeneic spleen cells (C3H/HeN) responded also positively to the soluble molecules we had isolated. Spleen cells that were treated with Concanavalin A and soluble MHC molecules increased the incorporation of radioactivity in an additive manner. Furthermore, during one way, Mixed Lymphocyte Reactions when Balb/c spleen cells that responded to inactivated with mitomycin C3H/HeN spleen cells, were treated with solution of soluble MHC II molecules, their responses were significantly boosted.
References
[1]van Rood JJ, van Leeuwen A, van Santen MCT: Anti-HL-A2 inhibitor in normal human serum. Nature (1970) Vol. 226(5243):366
[2] Jon J. van Rood and Aad van Leeuwen, Soluble HLA Antigens: How It All Started, Human Immunology (1999) Vol. 60:412–413
[3]Francesco Puppo Francesco Indiveri, Marco Scudeletti and Soldano Femme, ., Soluble HLA
antigens: new roles and uses, Trends in Immunology (1997), April (unspecified pages)
[4] Masao Hagihara, Tatsuo Shimura, Kozue Yamamoto, Kentaro Takebe, Batmunkh Munkhbat, and Kimiyoshi Tsuji, Soluble HLA Class I and Class II in Japanese, Human Immunology(1994) Vol. 40:
171-173
[5] Donnie Aultman, Irena Adamashvili, Kamalakar Yaturu, Marlyn Langford, Frank Gelder, Michael Gautreaux, G. E. Ghali, and John McDonald , Soluble HLA in Human Body Fluids, Human Immunology(1999) Vol. 60: 239–244
[6] Kerstin A. Pfeiffer, Vera Rebmann, Monika Passler, Kathrin van der Ven, Hans van der Ven,
Dieter Krebs, and Hans Grosse-Wilde , Soluble HLA Levels in Early Pregnancy After In Vitro
Fertilization, Human Immunology (2000) Vol. 61: 559–564
[7] Leon A. Verbruggen, Hendrik Versaen, Vera Rebmann, William Duquet, Seija De Cock, Hans
Grosse-Wilde, and Christian Demanet, Soluble HLA-DR Levels in Serum are Associated With Therapy and Genetic Factors in Rheumatoid Arthritis, Human Immunology (2002) Vol. 63: 758–764
[8] Wolf RE, Adamashvili IM, Gelder FB, Hall VC, Fraser PA, McDonald JC., Soluble HLA-I in Rheumatic Diseases Human Immunology(1998) Vol. 59: 644–649
[9] L.A. Verbruggen, N. Dumarey, H. Van de Velde,V. Rebmann, J. Flament, C. Van Wayenberge, H. Grosse-Wilde, C. Demanet, Soluble HLA-DR antigen levels in serum correlate with rheumatoid arthritis disease activity and the presence of disease-associated epitopes, Tissue Antigens (2000) Vol. 56: 436–440
[10] Andrea Steinborn, Vera Rebmann, Alexander Scharf, Christof Sohn, Hans Grosse-Wilde,, Soluble HLA-DR levels in the maternal circulation of normal and pathologic pregnancy, Am J Obstet Gynecol (2003) February: 473-479
[11] Roberta Rizzo, Cristina E. Mapp, Loredana Melchiorri, Piero Maestrelli, Annalisa Visentin, Stefano Ferretti, Ilaria Bononi, Deborah Miotto, Olavio R. Baricordi, Defective production of soluble HLA-G molecules by peripheral blood monocytes in patients with asthma, J Allergy Clin Immunol (2004) Vol. 115: 508-513
[12] Bishwajit Nag, Teresa Kendrick, Subhashini Arimilli, Sheue Ching T. Yu, Subramaniam Sriram, Soluble MHC II–Peptide Complexes Induce Antigen-Specific Apoptosis in T Cells, Cellular Immunology (1996) Vol. 170: 25 –33
[13] Webb BJ, Bochan MR, Montel A, Padilla LM, Brahmi Z., The lack of NK cytotoxicity associated with fresh HUCB may be due to the presence of soluble HLA in the serum, Cellular Immunology (1994) Vol. 159: 246-261
[14]Sofia Casares, Cong S. Zong, Dorel L. Radu, Alexander Miller, Constantin A. Bona, and Teodor-Doru Brumeanu, Antigen-specific Signaling by a Soluble, Dimeric Peptide/Major Histocompatibility Complex Class II/Fc Chimera Leading to T Helper Cell Type 2 Differentiation J. Exp. Med. (1999) Vol. 190: 543–553
[15]Abdel Rahim A. Hamad, Sean M. O’Herrin, Michael S. Lebowitz, Ananth Srikrishnan, Joan Bieler, Jonathan Schneck, Drew Pardoll Potent T Cell Activation with Dimeric Peptide–Major Histocompatibility Complex Class II Ligand: The Role of CD4 Coreceptor, J. Exp. Med. (1998) Vol. 188: 1633–1640
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