MHC class I molecules

This class of lymphocytes differentiates from immuno-logically incompetent hematopoietic stem cells of the bone marrow within the thymus - hence, the name thymus-dependent (T-) lymphocytes. Two major subclasses develop simultaneously, T-helper lymphocytes (Th) and cytotoxic effector lymphocytes (Tc). The cytotoxic T-lymphocytes (carrying on the surface the differentiation marker CD8) destroy cells, which cany their cognate antigen bound to MHC class I molecules on the surface by inducing apoptosis. From an evolutionary point of view Tc cells appear to have developed predominantly to cope with vims infections. As vituses can only replicate within cells, Tc eliminate them by destroying their producers. 

Class I. These molecules are expressed on the surfaces of all nucleated cells and are recognized by CD8+ cells, also known as cytotoxic T cells. There are three subclasses of MHC class I molecules called HLA-A, HLA-B, and HLA-C. 

Celia, H., Wilson-Kubalek, E., Milligan, R. A., and Teyton, L. (1999). Structure and function of a membrane-bound murine MHC class I molecule. Proc. Natl. Acad. Sci. USA 96, 5634-5639. 

Park, B., Lee, S., Kim, E., and Ahn, K. (2003) A single polymorphic residue within the peptide-binding cleft of MHC class I molecules determines spectrum of tapasin dependence. /. Immunol. 170, 961. 

CD8 + T cells are driven by MHC class I molecules and do not require professional APC. CD 45 Ro + CD8 + T cells are increased in early infection and are often maintained in symptomatic disease however, dendritic cells are important in stimulating cytotoxic T lymphocyte (CTL) responses in unprimed CD8 + T cell. CD8 cells may also be subdivided based on their cytokine secretion. CD8 CTL clones produce INF-y, IL-6, TNF-a, and ILIO, whereas suppressor cells produce high levels of cytokines associated with Th-2 cells, including IL-4 and low levels of IL-5, IL-6, and IL-10. 

Double negative (CD4-CD8-) TCR-ap-f Treg cells that mediate tolerance in several experimental autoimmune diseases have been described [ 111 ]. These double negative T cells are specific for MHC class I molecules and the suppressive effect of these cells on the proliferation and cytotoxic activity of CD8-I- T cells with the same antigen specificity was not mediated by cytokines, but instead was attributed to Fas-mediated apoptosis of alloreactive T cells [112]. 

POTENTIAL IMMUNE ESCAPE MECHANISMS OF TUMORS MHC CLASS I MOLECULES - ENEMIES OR FRIENDS... 

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. 

Peptides that serve as ligands for major histocompatibility complex (MHC) class I molecules can activate vomeronasal sensory neurons. These peptides contain nine amino acid residues and activate sensory neurons from the V2 receptor... 

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. 

Recognize viral peptide presented with MHC class I molecule on surface of infected cell. Kill by injecting enzymes and also by inducing apoptosis of infected cell. 

Defects in MHC Class II molecules, while exposing affected subjects to a variety of infections, do not result in the severe immunodeficiency seen in patients with SCID. In contrast to mutations affecting MHC Class II molecules, defects in MHC Class I molecules are rare. Mutations affecting MHC Class I molecules are directed to genes on chromosome 6 at the MHC locus that code for peptide-transporter proteins (122). The function of these transporter proteins is to transport the peptide antigens so that a complex with the a chain of MHC Class I molecules and p 2-microglobulin is formed and transported to the surface of the cell. 

There are a number of MHC class I and class II polymorphic molecules, all with substantially the same basic structure. The MHC class I molecule is a dimer consisting of a glycoslylated transmembrane peptide of molecular weight 45 kDa covalently linked to a 12 kDa peptide it is found on the surface of most nucleated cells within the body. It is believed that the polypeptide backbones fold in such as way as to form a platform of -pleated sheet structures to support a peptide binding cleft in which the antigen fragments are held and presented to the T cells. 

Parham, P. Ohta, T. (1996) Population biology of antigen presentation by MHC class I molecules. Science 272, 67-74. 

Eukaryotic cells also have additional transport mechanisms. One of these is an ABC transporter (p. 417) known as the transporter associated with antigen processing (TAP). It carries small polypeptides generated by proteasomes from the cytosol into the ER for export and binding to MHC Class I molecules and subsequent presentation to the immune system (Fig. 31-15).540 602... 

An additional line of defense is provided by natural killer cells (NK cells), a type of circulating lymphoid cell able to kill cancer cells, to participate in antiviral defenses, and to help control immune responses.273 -276 NK cells, which utilize their own signaling pathways, are also able to use MHC class I molecules to recognize and to spare the lives of normal, healthy cells.277/277a b Partial deprivation of a night s sleep can reduce NK cell activity, damaging the cellular immune response.278... 

---