Showing posts with label MHC protein. Show all posts
Showing posts with label MHC protein. Show all posts
TCR Signaling Pathway
T cell receptor is a complex of antigen specific alpha and beta chains associated in membrane CD3 gamma and CD3 delta,epsilon and zeta chains .
Each of the cd3 chains have at lest one copy of signaling motif immunoreceptor tyrosine activation motif or ITAMs in the cytoplasmic domain .various short family tyrosine kinase will associate with cytoplasmic domains in the Tcell receptor complex.
Fyn along with other short kinase family members are important for t cell activation,other molecules involved in T cell activation includes CD45 whose cytoplasmic domain contains tyrosine phosphatase enzyme and the T cell co receptor either CD4 or CD8.In this example the co receptor is CD4 ,the co receptor molecules have bound to cytoplasmic domains tyrosine kinase Lck,the cytosol enzyme ZAP70 also plays a essential role t cell activation.
Viral Evasions
When virusus infect a cell ,the proteins produced in the cytosol by the virus can be degraded by proteosome and trasported into ER though the TAP transporter ,the presence of these peptide in the ER allows them to loaded on to MHC class 1 molecules and evetully trasported to surface of the cell where it can be recognised by CD8 T cells .
Certain viruses are developed a stargeries to prevent their detection by cytotoxic t cells,Many of the statergies involve in preventing peptide derived from the virus from entering the ER and being loaded in MHC Class I molecules.
For example herpes simplex virus 1 codes a protein IPC47 that has ability to block peptide binding to the cytosol surface of the TAP transporter,In this way transport of viral peptides into the ER is prevented ,consequently these peptides cannot be loaded into MHC class I molecules.This results in reduced expression of peptide loaded MHC on surface of the infected cell.Cell is not killed and therfore virus can replicate sucessfully.
MHC Class 1 Protein
MHC class I proteins display short peptides, or antigens, derived from normal cell proteins. Peptide-loaded MHC proteins are located on the cell surface where they can be examined by passing T cells of the immune system. The MHC complex has two subunits. The smaller subunit, b2 microglobulin, resembles an immunoglobulin domain.
The larger a subunit also has an immunoglobulin-like domain which is linked to a head domain containing the antigen-binding groove. The antigen-binding groove in the MHC head domain is built from two walls composed of long alpha helices that rest on a floor composed of an eight stranded beta sheet. The peptide on display fits snugly between the helices in the groove.The peptide backbone is bound at both ends by highly conserved regions of the MHC protein. Some peptide side chains extend downwards into specific binding pockets in the groove, while other peptide side chains project upwards where they can be recognized by T cells. MHC class I proteins display their bound peptides on the cell surface for immune surveillance. Immune cells, called cytotoxic or killer T cells, for example, express T-cell receptors that bind to the MHC head domain and the bound peptide. If the cell expressing the MHC protein displays a peptide foreign to the immune system, the T cell is activated by this receptor-MHC interaction. The activated T cell then proceeds to destroy the abnormal cell. Cut-away views of this peptide-bound MHC protein complexed with a T-cell receptor reveal the exquisite precision with which the interacting surfaces fit together.
