MHC I protein

Antigen-specific reactions involving T cells, (a) Killer T cells interact and destroy target cells that display complexes of processed antigen with an MHC I protein. Effective interaction requires that the TCR... 

The MHC I protein contains two polypeptide ehains a and p. The a chain contains two distinct domains, a 1 and a2, that are on the outside surface of the antigen-presenting... 

Presentation of foreign (nonself) peptides by the MHC II protein to Th cells occurs in a similar manner to the MHC I proteins, requiring both the MHC II protein and T-cell surface proteins of the CD3 complex (see Table 35-1). The cell surface protein CD3 is involved in transmembrane signaling and initiation of cytokine (immune system messenger molecules) synthesis. Newly synthesized and recycled MHC II proteins are, like the MHC I proteins, ushered to the surface of the APC. 

FIGURE 14.15 Interaction between cytotoxic T cells (killer T cells) and antigen-presenting cells. Foreign peptides that are derived from the cytoplasm of infected cells are displayed on the surface by MHC I proteins. These bind to the T-cell receptor of a killer T cell. A docking protein called CDS helps link the two cells. 

Figure 15 MS/MS of a peptide extracted from the MHC-I protein HLA-A2.1 m/z 1121) following on-line capillary HPLC (estimated amount 0.1-0.3 pmol). The fragment ion spectrum obtained (b- and y-ion series) allows reading the sequence T(L/I)WVDPYEV, which matches a sequence of TIS21 (TLWVDPYEV), a member of the primary response group of genes induced by growth factors. The identity of the peptide was subsequently confirmed by chemical synthesis and comparative analyses. (From Ref. 53.)...

The major histocompatibility complex (MHC) is, in fact, a set of genes which code for three classes of proteins -class I, class II and class III. The class I proteins are involved in identifying cells that are infected with a virus. Class II proteins are involved in the interactions between Th cells and antigens. Class III proteins are the complement proteins. Although the name major histocompatibility complex actually refers to the genes,... 

MHC Class I proteins identification of cells infected with a virus... 

Figure 17.28 Killing of a virus-infected host cell by a cytotoxic T-cell. The protein synthetic machinery of the host cell is used to synthesise viral proteins. However, the protein of the virus is digested to produce peptides that form a complex with MHC class I protein, which is presented on the cell surface of the host cell, to which the cytotoxic T-cell binds, releasing the contents of the granules, which kill the host cell (see text).

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. 

Intracellular antigens could be modified internal proteins, which are continuously removed by the cell, the structure altered and attached to MHC I. This takes place in the rough endoplasmic reticulum. The protein/pep tide-hapten fragments are then presented to the external surface of the cell membrane as a complex with the MHC I. Then cytotoxic T cells (CD8+) accept the protein/peptide and destroy the cell. This mechanism gives rise to a type IV response. 

The resulting epitope density may depend on the number of lysine groups in the particular protein, and this will in turn affect the immunogenicity of the antigen. Trifluoroacyl adducts have been detected on the outer surface of hepatocytes, presumably as a result of the hapten-complex processing and delivery by MHC I, which is described above. The fact that the production of the trifluoroacetyl chloride is part of the major metabolic pathway and that the majority of patients produce trifluoroacylated proteins suggests that it is differences in the immune surveillance system or immune responsiveness, which determine which patients will succumb to the immunotoxic effect. 

TNF-a IL-1, IL-2, GM-CSF, LPS Tumor necrosis, endotoxic shock-like syndrome, cachexia, fever, acute-phase protein response IL-1, IL-6, GM-CSF, MHC I, MHC II Macrophages... 

CD8 CD10 CDllb TCR co-receptor binds to MHC-I metalloproteinase Zn-bound integrin Om associated with CD18 (integrin 32) CD54 ligand binds complement system iC3b and ECM (extracellular matrix) proteins also known as Mac-1... 

The protein encoded by the HFE gene is a 343-amino acid protein consisting of a 22-amino acid signal peptide, a large extracellular domain, a single transmembrane domain, and a short cytoplasmic tail (Fig. 31-2). As Figure 31-2 shows, the extracellular domain includes three loops (oij, a2, and a3) with intramolecular disulfide bonds within the second and third loops, a structure similar to other MHC class I proteins (Feder et al., 1996). 

Figure 31-2. Model of HFE protein. The HFE protein shares structural similarities to other MHC class I proteins.The locations of the two most common mutations are noted. Reprinted with permission Feder et al. (1996).

I. T Cell Receptors and MHC Class I Proteins Paradigms of Immunological Recognition... 

---