Professional Documents
Culture Documents
There are three major histocompatibility antigens; class I, classII, and class III MHC antigens .These antigens are genetically determined by a set of genes called the major histocompatibility gene complex , which lie on a portion of the short arm of human chromosome 6.These genes occupy four regions (A,B,C and D).
The major histocompatibility gene complex and the corresponding MHC classI and II molecules or antigens on the cell surface.
Regions B,C and A determine the antigenic specificities of class I MHC surface molecules. Region D determines the antigenic specificities of class II MHC surface molecules. The region between D and B codes for certain complement components ( C2,C4, factor B), and is not concerned with graft rejection. It is called class III MHC.
Class I MHC antigens: are glycoproteins and include HLA-A,HLA-B, and HLA-C. They are found on all nucleated cells. Class I MHC enables cytotoxic T cells (Tc) to recognize foreign antigen on the surface of graft cells, tumour cells or virus infected cells and kill these cells. In other words Tc cells (CD8)are triggered only when they recognize both antigen and class I MHC molecules in close association on the surface of cells. This is known as MHCrestriction.
Class II MHC-antigens: or HLA-D antigens are glycoproteins, and include HLA-DP, HLA-DQ and HLA-DR. These are found chiefly on the surface of antigen presenting cells (APCs) such as monocytes, macrophages, dendritic cells and B lymphocytes. Helper T cells (Th) (CD4) will recognize foreign antigen on the surface of APC only if they are associated with class II MHC molecules (MHC restriction).
HLA (MHC)
Class - I MHC 1-They include classical HLA- A ,B , C non classical HLA- G , E 2- Found on all nucleated cells
Class - II MHC 1-They include classical HLA- DP ,DQ , DR non classical HLA- DM, DO 2-Found on certain cells e.g. APCs. 3-Presents the Ag to Th
3-Presents the Ag to Tc
4-Determined by serologic tests 4-Determined by cellular tests e.g. Microcytotoxicity tests e.g. Mixed lymphocyte reaction
Both classes could be typed by: ELISA, Flow cytometry or molecular techniques such as PCR.
Importance of MHC
1.Organ transplantation and graft rejection. 2.MHC restriction: a) Tc cells recognize the Ag in association with MHC I. b) Th cells recognize the Ag in association with MHC II.
3.Disease association: It is found that the presence of certain HLA antigens is often associated with a particular disease; - HLA- B27 with ankylosing spondylitis. - B8 with myasthenia gravis. -DR2 with multiple sclerosis. -DR4 with rheumatoid arthritis
4.Paternity testing and forensic investigations ( An individual inherits one maternal and one paternal chromosome 6).