TY  - JOUR
AU  - Wang, Mingjun
AU  - Harhaji-Trajković, Ljubica
AU  - Lamberth, K
AU  - Harndahl, M
AU  - Buus, S
AU  - Heegaard, NHH
AU  - Claesson, MH
AU  - Nissen, Mogens H
PY  - 2009
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1463
AB  - Beta2-microglobulin (beta 2m) is the light chain of major histocompatibility complex class I (MHC-I) molecules, and is a prerequisite for the binding of peptides to the heavy chain and their presentation to CD8(+) T cells. beta 2m can be modified in vivo and in vitro by proteolytic cleavage by complement C1 and subsequent carboxypeptidase B-like activity - processes that lead to the generation of desLys(58)beta 2m (d beta 2m). This work aims to study the effect of d beta 2m on peptide binding to MHC-I, the influence of d beta 2m on the binding of beta 2m to the MHC-I heavy chain and the biological activity of d beta 2m. Both beta 2m and d beta 2m are able to support the generation of MHC-I/peptide complexes at 18 degrees C, but complexes formed in the presence of d beta 2m destabilize at 37 degrees C. Moreover, a 250 times higher concentration of d beta 2m than of beta 2m is needed to displace MHC-I associated beta 2m from the cell surface. In addition, only beta 2m is able to restore MHC-I/peptide complex formation on acid-treated cells whereas d beta 2m appears to bind preferentially to denatured MHC-I heavy chains. In cell cultures, exogenously added d beta 2m, but not beta 2m, induces apoptotic cell death in monocytic leukaemic cell lines but spares other kinds of leukaemic cells. Additionally, the presence of d beta 2m, and to a lesser extent beta 2m, enhances IFN-gamma-induced NO production by monocytic leukaemic cells. In conclusion, these data show that d beta 2m is not able to support the formation of a stable tri-molecular MHC-I complex at physiological temperature and that d beta 2m exerts other biological functions compared to beta 2m when bound to cells.
T2  - Scandinavian Journal of Immunology
T1  - Modified Human Beta 2-Microglobulin (desLys(58)) Displays Decreased Affinity for the Heavy Chain of MHC Class I and Induces Nitric Oxide Production and Apoptosis
IS  - 3
VL  - 69
EP  - 212
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1463
ER  - 

@article{
author = "Wang, Mingjun and Harhaji-Trajković, Ljubica and Lamberth, K and Harndahl, M and Buus, S and Heegaard, NHH and Claesson, MH and Nissen, Mogens H",
year = "2009",
abstract = "Beta2-microglobulin (beta 2m) is the light chain of major histocompatibility complex class I (MHC-I) molecules, and is a prerequisite for the binding of peptides to the heavy chain and their presentation to CD8(+) T cells. beta 2m can be modified in vivo and in vitro by proteolytic cleavage by complement C1 and subsequent carboxypeptidase B-like activity - processes that lead to the generation of desLys(58)beta 2m (d beta 2m). This work aims to study the effect of d beta 2m on peptide binding to MHC-I, the influence of d beta 2m on the binding of beta 2m to the MHC-I heavy chain and the biological activity of d beta 2m. Both beta 2m and d beta 2m are able to support the generation of MHC-I/peptide complexes at 18 degrees C, but complexes formed in the presence of d beta 2m destabilize at 37 degrees C. Moreover, a 250 times higher concentration of d beta 2m than of beta 2m is needed to displace MHC-I associated beta 2m from the cell surface. In addition, only beta 2m is able to restore MHC-I/peptide complex formation on acid-treated cells whereas d beta 2m appears to bind preferentially to denatured MHC-I heavy chains. In cell cultures, exogenously added d beta 2m, but not beta 2m, induces apoptotic cell death in monocytic leukaemic cell lines but spares other kinds of leukaemic cells. Additionally, the presence of d beta 2m, and to a lesser extent beta 2m, enhances IFN-gamma-induced NO production by monocytic leukaemic cells. In conclusion, these data show that d beta 2m is not able to support the formation of a stable tri-molecular MHC-I complex at physiological temperature and that d beta 2m exerts other biological functions compared to beta 2m when bound to cells.",
journal = "Scandinavian Journal of Immunology",
title = "Modified Human Beta 2-Microglobulin (desLys(58)) Displays Decreased Affinity for the Heavy Chain of MHC Class I and Induces Nitric Oxide Production and Apoptosis",
number = "3",
volume = "69",
pages = "212",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1463"
}

Wang, M., Harhaji-Trajković, L., Lamberth, K., Harndahl, M., Buus, S., Heegaard, N., Claesson, M.,& Nissen, M. H.. (2009). Modified Human Beta 2-Microglobulin (desLys(58)) Displays Decreased Affinity for the Heavy Chain of MHC Class I and Induces Nitric Oxide Production and Apoptosis. in Scandinavian Journal of Immunology, 69(3).
https://hdl.handle.net/21.15107/rcub_ibiss_1463

Wang M, Harhaji-Trajković L, Lamberth K, Harndahl M, Buus S, Heegaard N, Claesson M, Nissen MH. Modified Human Beta 2-Microglobulin (desLys(58)) Displays Decreased Affinity for the Heavy Chain of MHC Class I and Induces Nitric Oxide Production and Apoptosis. in Scandinavian Journal of Immunology. 2009;69(3):null-212.
https://hdl.handle.net/21.15107/rcub_ibiss_1463 .

Wang, Mingjun, Harhaji-Trajković, Ljubica, Lamberth, K, Harndahl, M, Buus, S, Heegaard, NHH, Claesson, MH, Nissen, Mogens H, "Modified Human Beta 2-Microglobulin (desLys(58)) Displays Decreased Affinity for the Heavy Chain of MHC Class I and Induces Nitric Oxide Production and Apoptosis" in Scandinavian Journal of Immunology, 69, no. 3 (2009),
https://hdl.handle.net/21.15107/rcub_ibiss_1463 .