Major Histocompability Complex (MHC)

1. Major Histocompability Complex(MHC) Anindyaningrum Chrisant Rystiasih Nadia Karlina *Protein images comparing the MHC I (1hsa) and MHC II (1dlh) molecules

2. What is MHC? Group of genes that code for proteins found on the surfaces of cells that help the immune system recognize foreign substances. MHC proteins are found in all higher vertebrates. In human beings the complex is also called the human leukocyte antigen (HLA) system.

3. MHC history • histocompatibility, derived from the Greek word histo (meaning “tissue”) and the English word compatibility • describe their function in transplantation reactions and does not reveal their true physiological function • In the 1950s skin graft experiments carried out in mice showed that graft rejection was an immune reaction mounted by the host organism against foreign tissue. The host recognized the MHC molecules on cells of the graft tissue as foreign antigens and attacked them. • Succesful transplant (organ/tissue) has as similar tissue type as possible

4. Key Words • Alleles: alternate forms of a gene that produce alternate forms of the protein • Tissue Type: set of MHC molecules of an individual • HLA: (human leukocyte antigens) proteins that are displayed on the cell surface and define an individual’s tissue type • complement system: a collection of soluble proteins found in the blood that targets foreign cells and breaks open their membranes (itu loh yg dijelasin sama Harvey & Elainne) • Killer T-Cell (lymphocyte) • Helper T-Cell (lymphocyte)

5. MHC Classifications • Class I • Class II • Class III Class I MHC molecules span the membrane of almost every cell in an organism class II MHC molecules span the membrane restricted to cells of the immune system called macrophages and lymphocytes. In humans these MHC molecules are encoded by several genes all clustered in the same region on chromosome 6. FYI: Each gene has an unusually large number of alleles (alternate forms of a gene that produce alternate forms of the protein). Thus, it is very rare for two individuals to have the same tissue type (whole set of MHC molecules of person) Also contains a variety of genes that code for other [complement proteins, cytokines (chemical messengers), and enzymes] they are called class III MHC molecules.

6. Class I • Are present on the membrane of almost every cell in an organism • job is to present fragments of proteins that are synthesized inside the cell. • Killer T-Cells/Cytotoxic T-Cells have the receptors for the class I MHC proteins, and check them periodically • Damaged/infected cells will display unfamiliar peptide antigens, e.g. fragments of viral proteins, and are attacked and destroyed • purpose is to identify abnormal body cells

7. Class II • Class II MHC proteins are found only on immune cells (found only on B lymphocytes, macrophages, and other cells that present antigens to T cells ) • These cells present peptide antigens derived from foreign digested particles (eg. From virus or bacteria) on the membrane • helper T-cells, which have receptors for class II MHC proteins will then stimulate immune response in B-cells. • Purpose: stop the immune system running out of control and attacking the body's own cells If the presented antigen is recognized as foreign by the helper T-cell (meaning it says to attack the foreign pathogen) then the phagocyte allowed to survive. If it presents a self antigen (meaning it would tell the other T-cells to attack the source of antigen, aka. Own body) the

8. MHC I -Self Cell MHC I Presenting Normal Protein Normal Cell Helper T Cell Check Self - OK

9. Cell MHC I - Virus Normal Cell MHC I Presenting Normal Protein Virus MHC I Presenting Defect Protein Virus Infected Cell Cell Helper T Cell MHC Checking Infected – Initiate Immune Response to Eliminatate Cell

10. B Cell MHC II – B Cell Antigen MHC II Presenting Self Protein Antibody Recognition Bacteria B Cell Phagocytosis B Cell Pathogen Degraded MHC II Presenting Foreign Protein B Cell Helper T Cell MHC Checking B Cell Targets Pathogen Helper T Cell Stimulate Antibody Production

11. MHC II – Killer T Cell Pathogen (Bacteria) Phagocyte Phagocytosis MHC II Presenting Foreign Protein Phagocyte Helper T Cell MHC Checking Non Self – Activate immune response Killer T Cell Helper T Cell Killer T Cell Attack Pathogen Killer T Cell

12. Conclusion Class I and II The class I and II MHC genes encode human leukocyte antigens (HLAs), proteins that are displayed on the cell surface and define an individual’s tissue type . There are many possible tissue types in the population because each HLA exists as a large number of varieties. Everyone's immune system is tolerant of its own HLAs, but if foreign HLAs are detected then the cells displaying them are attacked and destroyed. This is why the body rejects grafts and transplants from donors that have not been matched for tissue type.

13. Conclusion Class I and II • The class I and II MHC proteins also perform the important function of antigen presentation. This is how the immune system finds out what is happening inside our cells even though it can only survey them from the outside. Proteins inside the cell are broken into short fragments and displayed as peptide antigens by MHC proteins on the surface. This helps the immune system to discriminate between normal (self) antigens and those that are foreign and potentially dangerous.

14. Class III encode several components of the complement system, a collection of soluble proteins found in the blood that targets foreign cells and breaks open their membranes. Adjacent to the class III region is a group of genes that control inflammation. Further genes with various immune and non-immune functions are dotted throughout the complex.

15. MHC Genes Defects Defects in certain MHC genes lead to autoimmune disorders in which the body fails to recognize self-antigens. Ex. multiple sclerosis, some forms of arthritis and diabetes, and inflammatory bowel disease.

16. References • Twyman, Richard. "The major histocompatibility complex ". Wellcome Trust. 16 November 2009 <http://genome.wellcome.ac.uk/doc_wtd020754.html>. • "major histocompatibility complex (MHC)." Encyclopædia Britannica. 2009. Encyclopædia Britannica Online. 16 Nov. 2009 <http://www.britannica.com/EBchecked/topic/359034/major-histocompatibility-complex>.