Major Histocompatibility complex immune system and immune technology

Introduction, definition, history, types, procedure,main role, conclusion

1. Major histocompatibility complex

2. Synopsis Introduction. History. Definition. MHC Class I molecules. MHC class I molecules structure and function. MHC class II Molecules. MHC class II Molecules structure and function. Conclusion.

3. Introduction :The Major Histocompatibility Complex (MHC) is a group of genes that play a crucial role in the immune system. MHC molecules are responsible for: 1. Recognizing and presenting fragments of proteins (antigens) from pathogens, cancer cells, or self-proteins. 2. Activating immune responses by interacting with T-cells MHC molecules are like "identification cards" that help the immune system distinguish between: 1. Self (own body cells and proteins 2. Non-self (foreign substances, pathogens, or cancer cells) MHC molecules are divided into two main classes: MHC Class I (MHC-I): Expressed on all nucleated cells 2. MHC Class II (MHC-II): Expressed on antigen-presenting cells (APC ) understanding MHC is essential for 2. Transplantation3. Autoimmune diseases4. Infectious diseases5. Cancer immunology.

4. Introduction to MHC gene Introduction to MHC Genes: The Major Histocompatibility Complex (MHC) genes are a group of genes that encode MHC molecules, crucial for the immune system. These genes are responsible for: 1. Encoding MHC molecules that recognize and present antigens to T-cells. 2. Determining the ability of the immune system to recognize and respond to pathogens, cancer cells, and self-proteins. Key aspects of MHC genes: 1. Location: MHC genes are located on chromosome 6 in humans (HLA genes). 2. Polymorphism: MHC genes are highly polymorphic, with many variants, allowing for diverse immune responses. 3. Inheritance: MHC genes are inherited in a co-dominant manner, with both alleles expressed equally .

5. History History of Major Histocompatibility Complex (MHC): 1. *1900s*: Peter Gorer discovers the first MHC antigen in mice (1936) 2. *1950s*: MHC antigens are identified in humans (1958) by Jean Dausset and Rose Payne 3. *1960s*: The term "Major Histocompatibility Complex" is coined (1965) 4. *1970s*: MHC genes are mapped to chromosome 6 in humans (1970) 5. *1980s*: MHC class II genes are identified (1980) . Key milestones:- *1936*: Peter Gorer discovers the first MHC antigen in mice, leading to the understanding of transplant rejection.- *1958*: Jean Dausset and Rose Payne identify MHC antigens in humans, laying the foundation for human transplantation.- *1965*: The term "Major Histocompatibility Complex" is coined, recognizing the importance of MHC in immune responses.- *1980*: MHC class II genes are identified, revealing their role in antigen presentation.- *1990s*: Structural determination of MHC class I and II molecules reveals their mechanism of action.

6. Definition Definition of MHC Gene: Major Histocompatibility Complex (MHC) genes are a group of genes that encode proteins responsible for: 1. Recognizing and presenting fragments of proteins (antigens) from pathogens, cancer cells, or self-proteins to T-cells. 2. Activating immune responses by interacting with T-cells. MHC genes encode MHC molecules, which are:1. Cell surface proteins2. Highly polymorphic (many variants) 3. Essential for immune recognition and response .

7. Role of MHC in immune response. MHC (Major Histocompatibility Complex) plays a central role in the immune response by: 1. Presenting antigens to T-cells, activating immune responses. 2. Distinguishing self from non-self, preventing autoimmune diseases. 3. Regulating immune cell interactions and communication. 4. Influencing the type and magnitude of immune responses. MHC Class I:- Presents endogenously synthesized peptides to CD8+ T-cells.- Initiates cytotoxic T-cell responses against infected cells and tumors. MHC Class II:- Presents exogenously derived peptides to CD4+ T-cells.- Initiates helper T-cell responses, activating B-cells and cell-mediated immunity. MHC's role in immune response:1. Antigen presentation and recognition.2. T-cell activation and proliferation.3. Immune cell communication and coordination.4. Self-tolerance and prevention of autoimmune diseases.5. Immune response regulation and modulation. In summary, MHC is essential for initiating and regulating immune responses, protecting against infections and diseases while maintaining self-tolerance.

8. Classification MHC genes are classified into: 1. Class I genes (HLA-A, HLA-B, HLA-C): Encode MHC-I molecules, presenting endogenously synthesized peptides to CD8+ T-cells . 2. Class II genes (HLA-DRA, HLA-DRB, HLA-DQA, HLA-DQB, HLA-DPA, HLA-DPB): Encode MHC-II molecules, presenting exogenously derived peptides to CD4+ T-cells. 3. Class III genes (C2, C4, factor B, and others): Encode complement components and other immune-related molec ules .

9. Main role MHC genes play a critical role: Immune recognition and response Transplantation compatibility Autoimmune disease susceptibility Infectious disease resistance Cancer immunology In summary, MHC genes are essential for the immune system's ability to recognize and respond to antigens, and their polymorphism allows for diverse immune responses.

10. MHC class I Molecules Definition of MHC Class I Molecule: MHC Class I molecules are cell surface proteins responsible for presenting endogenously synthesized peptides (antigens) to CD8+ T-cells, triggering immune responses.

11. MHC class I Molecules structure MHC Class I Molecule Structure: The MHC Class I molecule consists of two subunits: 1. Heavy Chain ( α- chain): - 3 domains: α1, α2, and α3 - Transmembrane and cytoplasmic regions - α1 and α2 domains form the peptide-binding groove . 2. Light Chain ( β2- microglobulin ) : - Single domain - Non-covalently bound to the heavy chain - Stabilizes the heavy chain and peptide-binding groove . Peptide-Binding Groove: Formed by the α1 and α2 domains . Consists of two helices and a β- sheet floor . Peptide binds in the groove, with anchor residues at both ends . Key Features: α1 domain: peptide-binding site, polymorphic residues- α2 domain: peptide-binding site, polymorphic residues- α3 domain: Ig-like domain, interacts with CD8- β2- microglobulin : stabilizes the heavy chain, non-polymorphic- Transmembrane region: anchors the molecule to the cell membrane- Cytoplasmic region: interacts with cytoskeletal proteins. Dimensions : Length: approximately 350 amino acids (heavy chain) + 100 amino acids ( β2- microglobulin )- Width: approximately 50-60 Å (peptide-binding groove) .

12. Key features and dimensions Key Features:- α1 domain: peptide-binding site, polymorphic residues- α2 domain: peptide-binding site, polymorphic residues- α3 domain: Ig-like domain, interacts with CD8- β2- microglobulin : stabilizes the heavy chain, non-polymorphic- Transmembrane region: anchors the molecule to the cell membrane- Cytoplasmic region: interacts with cytoskeletal proteins . Dimensions :- Length: approximately 350 amino acids (heavy chain) + 100 amino acids ( β2- microglobulin )- Width: approximately 50-60 Å (peptide-binding groove)The MHC Class I molecule structure allows for specific peptide binding and presentation to CD8+ T-cells, enabling immune recognition and response.

13. MHC class I Molecules procedure MHC Class I Molecule Procedure: Step 1: Protein Synthesis*- Proteins are synthesized in the cytosol- Proteins can be self-proteins or foreign proteins (e.g., viral proteins) . Step 2 : Protein Degradation*- Proteins are degraded into peptides by proteasomes- Peptides are transported into the endoplasmic reticulum (ER) by TAP (transporter associated with antigen processing) . Step 3: Peptide Loading*- Peptides are loaded onto newly synthesized MHC Class I molecules in the ER- Peptides bind to the peptide-binding groove formed by the α1 and α2 domains. Step 4: MHC Class I Assembly*- Heavy chain ( α- chain) and light chain ( β2- microglobulin ) assemble in the ER- Chaperone proteins (e.g., calnexin , calreticulin ) assist in assembly and folding . Step 5: Quality Control*- MHC Class I molecules undergo quality control checks in the ER and Golgi apparatus- Incorrectly folded or assembled molecules are retained or degraded . Step 6 : Transport to Cell Surface*- MHC Class I molecules are transported to the cell surface through the Golgi apparatus- Molecules are anchored to the cell membrane by the transmembrane region . Step 7: Antigen Presentation*- Peptide-loaded MHC Class I molecules present antigens to CD8+ T-cells- CD8+ T-cells recognize and respond to the presented antigens . This procedure allows MHC Class I molecules to present endogenously synthesized peptides to CD8+ T-cells, enabling immune recognition and response.

14. Function MHC Class I Molecule Functions: 1. Antigen Presentation: Present endogenously synthesized peptides to CD8+ T-cells, triggering immune responses. 2. Immune Surveillance: Continuously monitor cells for signs of infection, cancer, or other abnormalities. 3. CD8+ T-cell Activation: Activate CD8+ T-cells to kill infected cells or produce cytokines. 4. Cellular Immunity: Play a central role in cellular immunity, working with CD8+ T-cells to eliminate infected cells. 5. Tumor Immuno surveillance: Recognize and present tumor antigens, helping to eliminate cancer cells.

15. 6 . Viral Immunity : Present viral antigens, helping to eliminate infected cells and control viral infections. 7. Self-Tolerance: Help maintain self-tolerance by presenting self-peptides, preventing autoimmunity. 8. Transplant Rejection: Play a role in transplant rejection, presenting alloantigen to T-cells. 9. Immune Regulation: Regulate immune responses, preventing excessive or inappropriate activation. 10. Cellular Stress Response: Respond to cellular stress, presenting stress-induced peptides to T-cells. MHC Class I molecules are essential for immune recognition and response, working with CD8+ T-cells to protect against infections, cancer, and other diseases.

16. MHC class II Molecules definition Definition of MHC Class II Molecules: MHC Class II molecules are cell surface protei ns responsible for presenting exogenously derived peptides (antigens) to CD4+ T-cells, triggering immune responses.

17. Structure MHC Class II Molecule Structure: Alpha ( α) Chain: 2 domains: membrane proximal ( α2) and distal ( α1)- α1 domain: peptide-binding site, polymorphic residues- α2 domain: Ig-like domain, interacts with CD4. Beta ( β) Chain: 2 domains: membrane proximal ( β2) and distal ( β1)- β1 domain: peptide-binding site, polymorphic residues- β2 domain: Ig-like domain, interacts with CD4. Peptide-Binding Groove Formed by the α1 and β1 domains- Consists of two helices and a β- sheet floor- Peptide binds in the groove, with anchor residues at both ends .

18. Key features and dimensions Key Features: Key 1 and β1 domains: peptide-binding site, polymorphic residues- α2 and β2 domains: Ig-like domains, interact with CD4- Transmembrane region: anchors the molecule to the cell membrane- Cytoplasmic region: interacts with cytoskeletal proteins Dimensions : Length: approximately 350 amino acids ( α- chain) + 350 amino acids ( β- chain)- Width: approximately 50-60 Å (peptide-binding groove)The MHC Class II molecule structure allows for specific peptide binding and presentation to CD4+ T-cells, enabling immune recognition and response.

19. Procedure MHC Class II Molecule Procedure: Step 1: Protein Uptake - Antigen-presenting cells (APCs) uptake extracellular proteins (e.g., bacterial proteins) through endocytosis . Step 2: Protein Degradation- Proteins are degraded into peptides by proteases in the endosomal compartment . Step 3: Peptide Loading - Peptides are loaded onto newly synthesized MHC Class II molecules in the endosomal compartment- Peptides bind to the peptide-binding groove formed by the α1 and β1 domains . Step 4: MHC Class II Assembly - Alpha ( α) and beta ( β) chains assemble in the endoplasmic reticulum (ER)- Chaperone proteins (e.g., invariant chain) assist in assembly and fold in . Step 5: Transport to Endosomal Compartment- MHC Class II molecules are transported to the endosomal compartment, where peptides are loaded . Step 6: Peptide Exchange- Invariant chain is replaced by the loaded peptide . Step 7: Transport to Cell Surface -Peptide-loaded MHC Class II molecules are transported to the cell surface . Step 8: Antigen Presentation - MHC Class II molecules present peptides to CD4+ T-cells- CD4+ T-cells recognize and respond to the presented peptides .

20. Function MHC Class II Molecule Functions: 1. P antigen Presentation: Present exogenously derived peptides to CD4+ T-cells, triggering immune responses. 2. Immune Activation l : Activate CD4+ T-cells to produce cytokines, activate B-cells, and coordinate immune responses. 3. Antigen Processing: Process and present antigens from extracellular proteins, such as bacterial proteins and toxins. 4 . T-Cell Activation: Activate CD4+ T-cells to initiate immune responses, including antibody production and cell-mediated immunity. 5. Imm une self-tolerance : Regulate immune responses by presenting self-peptides and maintaining self-tolerance.

21. 6. Disease Prevention: Help prevent autoimmune diseases by presenting self-peptides and maintaining self-tolerance. 7. Transplant Rejection : Play a role in transplant rejection by presenting alloantigen to T-cells. 8. Infectious Disease Immunity : Present antigens from infectious agents, such as bacteria and viruses, to initiate immune responses. 9. Cancer Immuno surveillance : Present tumor antigens to initiate immune responses against cancer cells. l 10. Immune Cell Communication :Facilitate communication between immune cells, including T-cells, B-cells, and antigen-presenting cells. MHC Class II molecules play a crucial role in initiating immune responses, maintaining self-tolerance, and preventing autoimmune diseases.

22. Conclusion In conclusion, the Major Histocompatibility Complex (MHC) is a vital component of the immune system, playing a central role in antigen presentation, immune recognition, and disease susceptibility. Its high polymorphism and association with various diseases make it a crucial area of study in immunology and medicine, with significant implications for vaccine development, transplantation medicine, and personalized healthcare.

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