Major histocompatibility degradation

Formation of antigens from the intracellular degradation of pathogens The proteolytic system hydrolyses proteins of pathogens that are present within the host cell (e.g. a virus), to produce a short peptide which forms a complex with a specific protein, known as the major histocompatibility complex (MHC) protein. The peptide is, in fact, the antigen. At the plasma membrane, the MHC protein locates within the membrane and the small peptide sits on the outside of the membrane, where it can interact with the receptor on a cytotoxic T-lymphocyte to kill the host cell and the virus (Chapter 17). 

APC, antigen-presenting cell and, class I and II major histocompatibility complex (MHC) antigens o and , peptides from degraded antigen bound to MFIC molecules ... 

At this point, the endosome may fuse with vesicles containing newly synthesized or recycling major histocompatibility complex (MHC) antigens. Some of the partially degraded antigenic fragments may form a complex with the MHC and be transported back to the cell surface. There they are presented to the circulating T-helper (Th)... 

Craiu, a., Gaczynska, M., Akopian, T, Gramm, C. F., Fenteany, G., Goldberg, A.L., Rock, K. L., Lactacystm and dasto-lactacystin beta-lactone modify multiple proteasome beta-subunits and inhibit intracellular protein degradation and major histocompatibility complex class 1 antigen presentation. J. Biol. Chem. 1997,... 

Moore, S. E. H. Spiro, R. G. (1993). Inhibition of glucose trimming by castanospermine results in rapid degradation of unassembled major histocompatibility complex class I molecules. J. Biol. Chem. 268, 3809-3812. 

Wilson, C.M., Farmery, M. R., and Bulleid, N. J. (2000). Pivotal role of calnexin and mannose trimming in regulating the endoplasmic reticulium-associated degradation of major histocompatibility complex class I heavy chain. T. Biol. Chem. 275, 21224-21232. 

The immune system also makes use of the ubiquitin-mediated pathway in the response to altered self-cells, particularly virus-infected cells. Viral proteins within the cytosol of infected cells are ubiquitinated and then degraded in pro-teasomes specially designed for this role. The resulting antigenic peptides are transported to the endoplasmic reticulum, where they bind to class I major histocompatibility complex (MHC) molecules within the ER membrane. Subsequently, the peptide-MHC complexes move to the cell membrane where the antigenic peptides can be recognized by c3rt otoxic T lymphocytes, which mediate the destruction of the Infected cells. 

Hughes EA, Hammond C, Cresswell P (1997) Misfolded major histocompatibility complex class I heavy chains are translocated into the cytoplasm and degraded by the proteasome. Proc Natl Acad Sci USA 94 1896-1901... 

Zhong G, Fan T, Liu L (1999) Chlamydia inhibits interferon gamma-inducible major Histocompatibility complex class II expression by degradation of upstream stimulatory factor 1. J Exp Med 189 1931-1938... 

Proteasomes are the major cytosolic and nuclear protein degradation machineries and they are also responsible for the proteolysis of misfolded, ER-dislocated (endoplasmic reticulum) proteins [1-3]. Proteasomal protein turnover takes place in an ubiquitin-dependent manner. The proteasome-generated products - ohgopeptides varying in length from 3 to up to 30 amino acid residues - are further processed by aminopeptidases. In higher vertebrates, antigenic peptides are selected from the peptide pool produced by proteasomes and downstream aminopeptidases for presentation on the outer cell surface by major histocompatibility class 1 (MHCl) protein complexes. In this way, proteasomes are essential factors in the detection and eradication of virally infected cells. 

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