Major Histocompatibility Complex


The major histocompatibility complex (MHC), otherwise known as the human leucocyte antigen (HLA) complex, is a set of surface molecules that are vital to allow T cells to function.

In simple terms they may be thought of as identity badges which identify a cell as belonging to the same host as the immune system. However, in addition to this ID card role they also let the immune system inspect the contents of the cell to look for intruders.

Two classes Of HLA molecule exist.

MHC Class One

Class one MHC molecules can colloquially be described as acting both as identity badges and distress signals. They are present on all cells that have nuclei and are encoded by HLA gene classes A, B and C.

If foreign proteins enter a cell, such as would occur if the cell was infected by a virus, enzymes and proteosomes inside the cell degrade these antigenic proteins. The fragments are complexed with MHC class one molecules in the endoplasmic reticulim of the cell and this complex is then transported to the surface of the cell where it can be detected by cytotoxic T cells. In this way, an infected cell can signal that is has been infected and alert the T cells that recognise that antigen to the presence of the intruder. Unfortunately for the cell the usual response of the T cell is to induce the infected cell to undergo apoptosis. Conversely, an uncomplexed MHC molecule informs that T cell that all is well and that the cell is friendly.

MHC Class Two

Class two MHC molecules have a much more restricted distribution than class one molecules. They are coded for by the D class of HLA genes. Several subclasses exist (DP, DQ, DR and DW).

Class two MHC molecules are usually only expressed on antigen presenting cells and B cells . Thus, the antigen they bring to the attention of T cells is derived mainly from the extracellular environment that the antigen presenting cell is sampling (exogenous antigen) rather than the intracellular environment that is handled by MHC class one molecules (endogenous antigen). Antigen that is complexed with MHC class two molecules is recognised by helper T cells. Activation of T helper cells can initiate a profound immune response so it is vital to ensure that it does not occur inappropriately. For this reason the antigen presenting cell keeps its intracellular MHC class two molecules in a 'clipped' state in which the antigen binding site is blocked. This clip is only released if the MHC molecule enters a phagolysosome that has engulfed extracellular antigen. This system prevents the MHC molecule from inadvertently becoming complexed with host antigens inside the antigen presenting cell.