Eng. major histocompatibility complex

Major Histocompatibility complex

1. MAJOR HISTOCOMPATIBILITY COMPLEX Dr. Renuka Hare Krishnan 1

2. MHC complex The MHC complex is a tightly- linked cluster of genes present in all mammalian species. The products (proteins) of these genes play an important role on intercellular recognition , ag presentation and discrimination between self and non-self by inducing both HI and CMI. Dr. Renuka Hare Krishnan 2

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8. MHC genes code for cell surface histocompatibility antigens are so polymorphic that virtually no two human beings have the same set of HLA antigens . Dr. Renuka Hare Krishnan 8

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10. The rejection of transplanted graft tissue between genetically non-identical individuals is brought about by the MHC antigens. Hence, the MHC molecules are also called as transplantation antigens. MHC molecules are classified into four classes, namely Class I MHC molecules Class II MHC molecules Class III MHC molecules and Class IV MHC molecules. Class I and Class II MHC molecules belong to the immunoglobulin super family. Dr. Renuka Hare Krishnan 10

11. Dr. Renuka Hare Krishnan 11 GENE ARRANGE MENT

12. Dr. Renuka Hare Krishnan 12 ß2 microglobulin is located on a different chromosome (15). GENE ARRANGE MENT

13. Genes of Mhc organized in 3 classes Dr. Renuka Hare Krishnan 13 CLASS I MHC GENES Glycoproteins found on all nucleated cells except RBCs. They present processed endogenous ag to Tc cells . CLASS II MHC GENES Glycoproteins found on APC – dendritic cells, macrophages, B cells and other cells. They present exogenous ag to T H cells . CLASS Iii MHC GENES Products that include secreted proteins that have immune functions. Eg. Complement system, inflammatory molecules- cytokines and heat shock proteins.

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15. ANTIGEN PROCESSING AND AG PRESENTATION Proteins present inside the cells are periodically broken down into short peptide fragments by appropriate enzyme mechanism (Ag processing). These peptide fragments are displayed as peptide antigens by MHC molecules on the surface of the cell (Ag Presentation) . MHC molecules display both self peptides derived from their own proteins and foreign peptides derived from invading pathogens if any. The IS constantly watch the surface of the cells for peptides presented by MHC and identifies the self ag and the foreign ag that are dangerous. The IS also monitors the amount of MHC presented ags , which helps to target and destroy cancer cells that often display increased amounts of self ags . Dr. Renuka Hare Krishnan 15

16. Among the 4 MHC classes, Class I and Class II MHC molecules are worked in ag presentation. MHC molecules always recognize only T lymphocytes. Class I MHC molecules are recognized by CD8+ receptor of cytotoxic T cells (Tc). Class II MHC molecules recognize CD4+ receptor of helper T cells (Th). Dr. Renuka Hare Krishnan 16

17. Structure of class I MHC molecule Class I MHC molecules consist of 2 poly peptide chains namely - chain and ß2 microglobulin . - chain is encoded by the BCA region of HLA and ß2 is encoded elsewhere. The MHC encoded pp is about 350 AAs long with total mol. Wt. of 45 Da. This PP folds into three separate globular domains called ß2 microglobulin is a 12 kDa PP that is non-covalently associated with the domain.   Dr. Renuka Hare Krishnan 17

18. Structure of class I MHC molecule There are 4 regions in MHC I: Peptide binding region - a groove formed from 1 and 2 domains of the chain. Immunoglobulin like region - highly conserved 3 domain, a site to which CD8 on Tc cell binds. Transmembrane region - stretch of hydrophobic amino acids spanning membrane. Cytoplasmic region – sites for phosphorylation and binding to cytoskeletal elements.   Dr. Renuka Hare Krishnan 18

19. Function of Class I mhc or endogenous pathway Class I MHC molecules present endogenous ags on the surface of all nucleated cells. They present peptides derived from cytosolic proteins. So, the pathway of class I MHC presentation of ags is often called as cytosolic or endogenous pathway. It can also present peptides generated from exogenous proteins through cross presentation. Dr. Renuka Hare Krishnan 19

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21. Class I mhc /endo genous path way Dr. Renuka Hare Krishnan 21

22. Structure of class II mhc molecule Class II MHC molecules are found only on a few specialized cell types, including macrophages, dendritic cells and B cells, of all which are professional ag- presenting cells (APCs). It binds with the exogenous (endocytic degradation) antigens. It binds with CD4+ adhesion molecules of T H cells. Dr. Renuka Hare Krishnan 22

23. Structure of class II mhc molecule Dr. Renuka Hare Krishnan 23

24. Class II mhc / exo genous path way Dr. Renuka Hare Krishnan 24

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28. Cross presentation Dr. Renuka Hare Krishnan 28

29. Role of cross presentation Cross presentation is necessary for immunity against tumors. It is necessary for immunity against viruses that do not infect APCs. Eg. Herpes virus, Influenza virus. It is required for the induction of cell mediated immunity by vaccination. Eg. Tumor vaccines. It avoids viral immune evasion strategies such as suppression of antigen processing. It provides immune defense against bacteria. Eg. Mycobacterium tuberculosis, E. Coli. Dr. Renuka Hare Krishnan 29

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33. Functions of MHC Induce the differentiation and maturation of T cell to form functional T cell repertoire. Present ag to initiate immune response with a phenomena known as MHC restriction. Endogenous ag is presented to CD8+ of Tc cell by MHC class I molecule. Exogenous ag is presented to CD4+ of TH cell b MHC class II molecule. Participant in both humoral and cell-mediated immunity. Discriminate self and non-self ags . They mediate autoimmune diseases. They bring about graft rejection. They provide defense against infections and diseases. Paternity testing. They are responsible for individual smell of people. Important in determining the compatibility of tissues in successful grafting between donor and recipient. Anthropology to study races and nations. Dr. Renuka Hare Krishnan 33

34. MCQ 1. T cells recognise antigen a)  In a 3 dimensional form b)  In solution in the plasma c)  When presented on the surface of antigen presenting cells d)  Following presentation by pattern recognition receptors 2. Major histocompatibility complex is a tight cluster of linked___________ a) carbohydrates b) proteins c) genes d) lipid molecules 3. What is the name of mhc in humans? A) HLA b) H2 c) adjuvants d) haplotype 4. Which of the following polypeptide is important for the expression of MHC I on the cell membrane? a) Interferons b) β2-microglobin c) Lymphokines d) Interleukins 5 . Which of these are non-professional antigen presenting cells? a) macrophages b) dendritic cells c) fibroblast d) B lymphocytes 6. Name the cell which receives antigen presented by MHC molecule. a) NK cells b) B-cells c) T-cells d) Macrophages 7. Name the class of MHC which is recognized by CD4 TH cell. a) MHC cannot recognize T cells b) MHC III c) MHC I d) MHC II 8 . Which MHC molecule recognizes CD8 TC cells? a) MHC I b) MHC II c) MHC III d) HLA-C ANSWERS: 1 C, 2 C , 3 A, 4 b, 5 c 6 c, 7 d, 8 a Dr. Renuka Hare Krishnan 34

35. Dr. Renuka Hare Krishnan 35 THANK YOU