MHC major histocompatibility complex
- 1. S U B M I T T E D T O - S U B M I T T E D B Y - M R . N A V I S H M A T H U R A D I T I B A G D I A S S I S T A N T P R O F E S S O R A T M S B T 1 S T S E M . L A C H O O M E M O R I A L C O L L E G E B I O T E C H N O L G Y O F S C I E N C E A N D T E C H N O L O G Y J O D H P U R COLLEGE OF SCIENCE AND TECHNOLOGY
- 3. Contents- Introduction History Types of MHC molecule Structure of MHC molecule HLA (Human Leukocyte Antigen) H-2 complex (MHC of mouse) Peptide MHC Interaction Function of MHC Summary of MHC molecule References
- 4. Introduction- Major Histocompactibility complex (MHC) is set of surface proteins located on the cell membrane of nucleated cells. It plays more important work to indentify the antigen between self and non self body, intracellular recognization and responsible for antigen presentation. Histo refers to tissues. Compatibility refers to living together harmoniously.MHC molecules always recognize only T lymphocytes. The two types of MHC are worked in immunity. T helper (Th) cell recognized by MHC molecules II, and T cytotoxic (TC) cells are recognized by MHC I molecules. Definition• "Major Histocompactibility complex is membrane attached protein which work on recognization of antigen between self and non self body and antigen presentation"
- 5. History- George Snell(1903-1996) discovered the first components of the MHC through their role in rejecting transplants in mice, and created the word “histocompatibility”. Around a decade later, Jean Dausset(1916- 2009)uncovered the first compatibility antigen in humans. Experiments by Baruj Benacerraf (1920- 2011) in the 1970s provided the first indication that immune reactions are controlled by the MHC genes ('immune response genes').
- 6. Classes of MHC molecule- The MHC molecules are classified into four classes namely- Class I MHC molecules Class II MHC molecules Class III MHC molecules Class IV MHC molecules
- 7. Class I MHC molecule- Class I MHC (45 KD) molecule are a group of major histocompactibility antigen. They are present the surface of all nucleated cells except nervous tissue and platelets. It present antigen to Te cells. It bind with CD-8 adhesion molecules of Te cells. It brings about cell mediated immune response.
- 8. Structure of MHC I molecule- It consists two polypeptide chains namely a chain and B2 - micro globulin. a chain which is non covalently attached with B2 microglobulin. a chain contain a transmembrane glycoprotein which is encoded by A,B and C gene of grouped HLA a chain is organized by three domains such as a 1, a 2 and a 3 each domain containing 90 amino acids sequences.B2 microglobulin is similar in size of a 3 and it dose not contain trans membrane proteins. When the antigen is internalized and processed inside by proteosome (Ubiquitin, cytosolic degradation), the peptides are produced. Peptide is further loaded on the groove of MHC I molecules from endoplasmic reticulum.
- 10. Class II MHC molecule- Class II MHC molecule are present on the surface of antigen presenting cell and cell which engulfed the foreign antigen. It binds with the exogenous (endocytic degradation ) antigens. It binds with CD4 adhesion molecules TH cells.• It also consist of two polypeptide chains namely a chain and ß chain. Antigen is processed inside the endosome and peptide is further loaded on groove of MHC II molecules.
- 11. Structure of MHC II molecule- The class II MHC Molecule consists of two polypeptide chain namely a chain (33 kDa) and B (28kDa) chain. The both chain are attached noncovelantly. Each chain contains two units. The two units of a chain are called al and a2. The two domains of B chains are called B1 and B2. 32 and a2 are transmembrane domains anchoring the MHC to plasma membrane. The al and B1 domains jointly bear a peptide binding groove.
- 13. Class III MHC molecule The molecules include complements like C2 and C4 and Bf (factor B). Class IV MHC molecule These molecule is present on T cells of leukemia (Tla) as well as on immature thymocytes.
- 14. HLA- Human Leukocyte Antigen- HLA is the human leukocyte antigen. HLA is the MHC molecules present in human beings. HLA is a set of surface protein present on the surface of all nucleated cells. They are responsible for graft rejection, adaptive immunity, defense against infection, some time it is expressed on cancer cell destruction, certain autoimmune diseases and certain complements. MHC is the general term referring to the cell surface antigen of vertebrates.
- 15. HLA complex spans 3.5 million bp on the short arm of chromosome 6
- 16. Classical HLA- Class I HLA-A,-B and–C loci Encode the heavy chain (α chain) of HLA class I molecule. Class II HLA-DP,- DQ, and DR Each has loci A and B, encode the α chain and β chain of HLA class II molecule, respectively.
- 17. Function of HLA molecule- Antigen presentation Process : endogenous antigen and exogenous antigen Presentation: TCR recognize MHC :peptide complex (double recognition) MHC restriction of T cell : Any individual’s T cells respond to a specific MHC allele expressed by that individual, that is to “self” MHC. others Genetically regulator of immune response, so to predispose individuals to particular susceptibility or disorders. Immune regulation.
- 18. H-2 complex of mouse- The major histocompactibility complex (MHC) of mouse is called H-2 complex. H-2 complex is a cluster of genes responsible for the production of antigens located of nucleated cells and complement components. This complex is located in the short arm of the chromosome number 17. It consists of a set of structural genes. The genes, that make up a given histocompatibility complex, are called halotypes
- 19. Peptide MHC Interaction- Peptide-binding groove of MHC Class I α 1 and α2 domains form peptide-binding domains Anti parallel eight stranded β-pleated sheet form the floor Two long α helices, oriented adjacent and roughly parallel to each other form sides of the deep cleft. Closed ends, accommodate about 8-11 aa in a flexible, extended conformation.
- 20. Peptide binding to Class I MHC Solvent Accessibility About 80% Buried. Size does matter. ( 9 mers best. )
- 21. Peptide-binding groove of MHC Class II •Two long α helicesas sides and theβ sheet as bottom •The ends of class II peptide-binding cleft are more open, bind longer and irregular peptides (12-16 aa be optimal)
- 25. MHC-Peptide Interaction- There are about a dozen of types of classical HLA molecules on the cell surface for one individual. However, there are much, much, much more kinds of antigen peptides would be presented in one individual. So, one type of HLA molecule can present large number of different peptides? • Some amino acid residues of peptide sanchor the peptide into the pockets within the groove of the MHC molecule, called anchor residue. So, • A given MHC molecule binds a group peptides with same anchor residues • The different MHC molecules bind different groups of peptides.
- 26. Class I MHC Elution of peptides. Anchor Residues.
- 27. Function of MHC molecule- MHC molecules are loaded with a bit of sample peptide fragment derived from the degradation of proteins present inside the cell. This peptide is the mirror image of proteins present inside the cell. MHC molecules contain self as well as nonself (foreign)antigen. They bring about defense against infections and diseases. They mediate certain autoimmune diseases. They are responsible for individual smell of people. Provide the strongest barrier for transplantation. Play a central role in generation and execution of immune response (presentation of peptide antigen to T cells). Susceptibility to infectious diseases and development of autoimmune diseases.
- 28. Summary of MHC- The both MHC I and II molecule are responsible for antigen presentation and it has application of antigen recognization between self and nonself recognization, mostly they are located on T lymphocytes encoded by chromosome 6 of the human. The two types of antigen degradated peptides (exogenous and endogenous) are involved to complete these process of antigen neutralization.
- 29. References- Judy Owen, Jenni Punt, Sharon Stranford. 2013. Kuby immunology. 7th edition. W.H. Freeman & Company. New York. NY 10010. Page no. 161-184. Fatima Dulsy & Arumugam N., Immunology (2013), 4th edition, Saras Publication, Camp Road Periavilai, Kanyakumari. Page no- 481-502.2