Structural Biochemistry/Protein function/Major Histocompatibility Complex (MHC)/MHC Class I

Class I MHC molecules

The Class I MHC molecules are found on all nucleated cells in the body (including cells expressing Class II MHC such as antigen presenting cells, dendritic cells, macrophages, and B cells), but are not found on non-nucleated cells such as red blood cells. It is found extending from the plasma membrane of body cells that have been infected with a virus or are otherwise abnormal (for example, cancerous). MHC Class I proteins bind to foreign antigen fragments (peptides) that are derived from intracellular proteins. For example, any cell that can become infected with a form of cancer will synthesize foreign antigens and then present them on the surface of the cell by the MHC I molecule. The T cell receptor of a Cytotoxic T cell that recognizes the MHC I-peptide complex binds to it with the aid of CD8, a protein found on the surface of cytotoxic T cells. This activates the cytotoxic T cell, stimulating its release of perforin, which increases permeability of the target cell membrane, and granzymes, which enter the target cell and initiate apoptosis, killing the target cell and fragmenting both its DNA and that of the virus. The cytotoxic T cell then detaches from the MHC I molecule and proliferates forming active cytotoxic T cells, which attack other infected body cells expressing the same antigen fragment, and memory cytotoxic T cells which will help produce a faster response to the virus if it attacks again.

Properly functioning MHC I molecules are essential in fighting cancer. That is, the immune cells of a person with defective MHC I molecules would not be able to recognize that cells had become cancerous, so no immune response would take place.

The interaction of T cells with antigen-presenting cells
1 A fragment of foreign protein (antigen) inside the cell associates with the components of an MHC molecule on the endoplasmic reticulum and is transported to the cell surface
2 The combination of MHC molecule and antigen fragment is recognized by a cytotoxic T cell
3 Cytotoxic T cells kill the infected cell.

File:MHC1.gif

The crystal structure of 2DD MHC class I in complex with the HIV-1 derived peptide P18-110.