Class peptide complexes

I MHC-peptide complexes and those that recognize class 11 MHC-peptide complexes utilize the same set of Va and Vp genes, and the principal feature that defines the site of class 1 MHC-TCR interaction, the cleft formed by the a and az subunits of the MHC molecule, is shared by both class 1 and class... 

Imai Y, Fujimori Y, Nakanishi K Basophils contribute to TH2-IgE responses in vivo via IL-4 production and presentation of peptide-MHC class II complexes to CD4+ T cells. Nat Immunol 2009 42 10 706-712. 

During the last decade the MHC class 1 antigen processing machinery (APM) has been well defined and appears to be more complex than initially expected. It consists of four major steps (i) peptide generation and peptide trimming, (ii) peptide transport, (iii) MHC class 1 assembly and (iv) presentation of the trimeric MHC class 1 heavy chain/p2-m/peptide complex on the cell surface (Eigure 1). 

The process is as follows a piece of DNA, which encodes a gene for a surface protein of the virus, is incorporated into a plasmid. From a suitable vector, DNA is taken up by host cells and incorporated into their DNA. A large amount of viral protein is produced within the host cell, hydrolysed and the resultant peptide complexed with MHC class I molecules presented on the cell surface. This is then seen and responded to by the Th cells which proliferate and form memory cells that will result rapidly in the death of host cells infected by the virus in subsequent infections. DNA vaccines are safer than live-virus vaccines and, furthermore, several genes that produce different viral antigens can be constracted on the same piece of DNA. 

MHC-class I proteins Some microorganisms have developed a considerable number of tricks to interfere with the presentation of the MHC-class I protein peptide complex on the surface of the infected host cell for example, production of a protein that binds the MHC protein and causes it to be retained within the endoplasmic reticulum. 

The path that leads from full sized protein to epitopes at the cell surface is complex, consisting of the generation of small peptides, translocation of the peptides to the endoplasmic reticulum by a transporter complex, loading of the peptides onto MHC class-I molecules and relocation of the MHC class-I-peptide complex to the cell surface (Rock and Goldberg, 1999). Since many of these steps are known to be prime targets for viral evasion strategies, the next step was to identify at what point the GAr interferes with the presentation of EBNAl. 

Interference in the transport of peptide antigens due to the absence of transporter proteins results in the destruction of the MHC Class I complex in the cytoplasm (123). Immunodeficiency resulting in mutations affecting MHC Class I complex assembly is not severe. 

To initiate a T-cell immune response, antigen presenting cells have to display antigenic peptides com-plexed with the major histocompatibility complex (MHC) on their cell surface. The T-cell receptor of CDS cells is specific for the peptide-MHC class I complex while the CD4 cell receptor binds the peptide-MHC class II complex. This binding of the peptide-MHC II complex stimulates CD4 cell proliferation and subsequent lymphokine release. This CD4 cell response can initiate a delayed hypersensitivity reaction. However CD4 activation and the production of various lymphokines is also needed for the generation of cytotoxic T-cells and for the differentiation of plasma cells from B-lymphocytes and the antibody response by these plasma cells. For their role in also the humoral immune response CD4 cells are called T-helper cells. 

Marine organisms are a well-established source of unique and biologically active peptides. Complex cyclic peptides and depsipeptides have emerged as an important new class of metabolites present in extracts of marine organisms. Many of these peptides have been found to be extremely potent cytotoxic and /or enzyme inhibitors. 

Andre, F., Chaput, N., Schartz, N.E., Flament, C., Aubert, N., Bernard, J., Lemonnier, F., Raposo, G., Escudier, B., Flsu, D.Fl., Tursz, T., Amigorena, S., Angevin, E. and Zitvogel, L. (2004) Exosomes as potent cell-free peptide-based vaccine. I. Dendritic cell-derived exosomes transfer functional MHC class 1/peptide complexes to dendritic cells. J. Immunol. 172, 2126-2136. 

Hiltbold, E.M., Poloso, N.J. and Roche, PA. (2003) MHC class Il-peptide complexes and APC lipid rafts accumulate at the immunological synapse. J. Immunol. 170, 1329-1338. 

The BCR mediates antigen uptake for processing and presentation of the antigeiuc peptide-MHC class II complex to T cells. 

The groove can be filled by a peptide from 8 to 10 residues long in an extended conformation. As we shall see (Section 33.5.6). MHC proteins are remarkably diverse in the human population each person expresses as many as six distinct class I MHC proteins and many different forms are present in different people. The first structure determined, HLA-A2, binds peptides that almost always have leucine in the second position and valine in the last position (Figure 33.25). Side chains from the MHC molecule interact with the amino and carboxyl termini and with the side chains in these two key positions. These residues are often referred to as the anchor residues. The other residues are highly variable. Thus, many millions of different peptides can be presented by this particular class I MHC protein the identities of only two of the nine residues are crucial for binding. Each class of MHC molecules requires a unique set of anchor residues. Thus, a tremendous range of peptides can be presented by these molecules. Note that one face of the bound peptide is exposed to solution where it can be examined by other molecules, particularly T-cell receptors. An additional remarkable feature of MHC-peptide complexes is their kinetic stability once bound, a peptide is not released, even over a period of days. 

Figure 33.30. T-Cell Activatiou. The interaction between the T-cell receptor and a class I MHC-peptide complex results in the binding of CDS to the MHC protein, the recruitment of the protein tyrosine kinase Lck, and the phosphorylation of tyrosine residues in the ITAM sequences of the CD3 chains. After phosphorylation, the ITAM regions serve as docking sites for the protein kinase ZAP-70, which phosphorylates protein targets to transmit the signal.

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