Antigen process and presentation and then MHC Molecules and functions

Antigen process and presentation, pepdidase and protease functions,cross presentation and then diagram.

1. ANTIGEN PROCESS and presentation

2. Content Introduction Definition What is MHC Molecules ? Function of MHC Molecules Structure of MHC Molecules Role of Pepdidase and protease Types of pathway Antigen process Antigen presentation Cross presentation Difference between class 1 MHC Molecules and class 2

3. Introduction ANTIGEN PROCESS Definition : Antigen processing is an immunological process that prepares antigens for presentation to T lymphocytes, a special type of immune system cell. It’s also known as the cytosolic pathway. ANTIGEN PRESENTATION Definition : Antigen presentation is a vital immune process that’s the first stage of the immune response. It involves antigen-presenting cells (APCs) such as macrophages and dendritic cells (DCs) taking up and processing pathogens like bacteria and viruses into antigenic peptides. These peptides are then transported to the cell surface and presented to T cells, which recognize only fragmented antigens. The outcome of antigen presentation is determined by the Major Histocompatibility Complex (MHC) molecules involved.

4. Major Histocompatibility (MHC) Major Histocompatibility Complex is also known as MHC. MHCs are essential for adaptive immunity . They are required to present antigen for the recognition by T cells . They are a set of genes coding for the surface proteins required to identify foreign antigens. In humans, the HLA (Human leukocyte antigen) complex works similar to MHC. There are two classes of MHC complex – Class I and Class II. Function of MHC Molecule : The function of  MHC molecules  is to bind peptide fragments derived from pathogens and display them on the cell surface for recognition by the appropriate  T cells . The consequences are almost always deleterious to the pathogen—virus-infected cells are killed, macrophages are activated to kill  bacteria  living in their intracellular vesicles, and B cells are activated to produce antibodies that eliminate or  neutralize  extracellular pathogens. Thus, there is strong selective pressure in favor of any pathogen that has mutated in such a way that it escapes presentation by an MHC molecule

5. MHC-I and MHC-II molecules have a very similar structure . In each case, a cleft or groove is formed that cradles the pep-tide. The charge characteristics of the groove determine which peptides can be presented

6. Proteolytic degradation : Proteolysis is the primary mechanism used by all cells not only to dispose of unwanted proteins but also to regulate protein function and maintain cellular homeostasis. Proteases that reside in the endocytic pathway are the principal actors of terminal protein degradation. The proteases contained in the endocytic pathway are classified into four major groups based on the active-site amino acid used by the enzyme to hydrolyze amide bonds of proteins: cysteine, aspartyl, serine, and metalloproteases. The presentation of peptide antigens by major histocompatibility complex (MHC) class II molecules is strictly dependent on the action of proteases. Class II molecules scour the endocytic pathway for antigenic peptides to bind and present at the cell surface for recognition by CD4+ T cells. The specialized cell types that support antigen presentation by class II molecules are commonly referred to as professional antigen presenting cells (APCs), which include bone marrow-derived B lymphocytes, dendritic cells (DCs), and macrophages. In addition, the expression of certain endocytic proteases is regulated either at the level of gene transcription or enzyme maturation and their activity is controlled by the presence of endogenous protease inhibitors.

7. Role of protease and pepdidase Protease : Proteases play a crucial role in antigen processing and presentation by:
1. _Breaking down proteins_: Proteases degrade proteins into smaller peptides, making them suitable for loading onto MHC molecules.
2. _Generating epitopes_: Proteases create specific epitopes (regions) on the peptide that can be recognized by T-cells.

3. _Influencing antigen presentation_: Proteases can affect the efficiency and outcome of antigen presentation, impacting immune response Types of proteases involved : 1. _ Endopeptidases _: Break proteins into smaller peptides (e.g., cathepsin B, cathepsin D). 2. _ Exopeptidases _: Trim peptides to optimal length for MHC loading (e.g., aminopeptidases, carboxypeptidases). 3. _ Dipeptidyl peptidases _: Remove dipeptides from the peptide's N-terminus (e.g., cathepsin C).

8. Peptidase : Peptidases play a crucial role in antigen processing and presentation by: Trimming peptides: Peptidases remove excess amino acids from the peptide's N- or C-terminus, optimizing its length for MHC loading. 2. Generating optimal epitopes: Peptidases create specific epitopes on the peptide, enhancing T-cell recognition . 3. Influencing antigen presentation: Peptidases affect the efficiency and outcome of antigen presentation, impacting immune responses. Types of peptidases involved :1. Aminopeptidases: Remove amino acids from the peptide's N-terminus (e.g., ERAAP, IRAP). 2. Carboxypeptidases_: Remove amino acids from the peptide's C-terminus (e.g., cathepsin B). 3. _Dipeptidyl peptidases_: Remove dipeptides from the peptide's N-terminus (e.g., cathepsin C)

9. ANTIGEN process Types of pathway Cytosolic or Endogenous pathway Exogenous or Endocytic pathway Cross presentation

10. Antigen prOcess Steps of cytosolic pathway : 1. Proteolytic Degradation of antigen into Peptides 2. Transportation of Peptides from cytosol to RER 3. Assembly of Peptides with class 1 MHC molecules. Antigen processing in MHC Molecules class 1

11. Antigen processing Antigen Processing Before an antigen can be presented, it must first be  processed . Processing transforms proteins into antigenic peptides. MHC Class I Molecules Intracellular  peptides for MHC class I presentation are made by proteases and the proteasome in the cytosol, then transported into the endoplasmic reticulum via TAP (Transporter associated with Antigen Processing) to be further processed. They are then assembled together with MHC I molecules and travel to the cell surface ready for presentation.

12. MCH Class II Molecules The route of processing for  exogenous  antigens for MHC class II presentation begins with endocytosis of the antigen. Once inside the cell, they are encased within endosomes that acidify and activate proteases, to degrade the antigen. MHC class II molecules are transported into  endocytic vesicles  where they bind peptide antigen and then travel to the cell surface. https://slideplayer.com/slide/7361146/

13. Antigen presentation Antigen Presentation Antigens are delivered to the surface of APCs by  Major Histocompatibility Complex  (MHC) molecules. Different MHC molecules can bind different peptides. The MHC is highly polygenic and polymorphic which equips us to recognise a vast array of different antigens we might encounter. There are different classes of MHC, which have different functions: MHC class I  molecules are found on all nucleated cells (not just professional APCs) and typically present  intracellular  antigens such as viruses. MHC class II  molecules are only found on APCs and typically present  extracellular  antigens such as bacteria. This is logical because should a virus be insiadde a cell of any type, the immune system needs to be able to respond to it. This also explains why pathogens inside human red blood cells (which are non-nucleated) can be difficult for the immune system to find, such as in malaria. Whilst this is the general rule, in  cross-presentation  extracellular antigens can be presented by MHC class I, and in  autophagy  intracellular antigens can be presented by MHC class II.

14. ANTIGEN PRESENTATION Antigen presentation is the process by which antigens are displayed on the surface of cells for recognition by the immune system. Here's a simplified overview:1. Antigen uptake: Cells engulf and digest foreign substances, breaking them into smaller pieces (antigens).2. Processing: Antigens are processed into smaller peptides and loaded onto MHC (Major Histocompatibility Complex) molecules.3. Presentation: MHC-peptide complexes are transported to the cell surface and displayed for recognition by T- cells.Types of Antigen Presentation:1. MHC Class I: Presents endogenously synthesized peptides (e.g., viral proteins) to CD8+ T-cells.2. MHC Class II: Presents exogenously derived peptides (e.g., bacterial proteins) to CD4+ T-cells.

15. Cross presentation Cross-presentation  is the ability of certain professional  antigen-presenting cells  (mostly dendritic cells) to take up, process and present  extracellular  antigens with  MHC class I  molecules to  CD8 T cells  (cytotoxic T cells). Cross-priming, the result of this process, describes the stimulation of naive  cytotoxic  CD8 +  T cells into activated cytotoxic CD8 +  T cells. This process is necessary for immunity against most tumors  and against viruses that infect dendritic cells and sabotage their presentation of virus antigens.Cross presentation is also required for the induction of cytotoxic immunity by  vaccination  with protein antigens, for example,  tumour vaccination . Cross-presentation is of particular importance, because it permits the presentation of exogenous antigens, which are normally presented by MHC II on the surface of dendritic cells, to also be presented through the MHC I pathway.[6] The MHC I pathway is normally used to present endogenous antigens that have infected a particular cell. However, cross presenting cells are able to utilize the MHC I pathway to present exogenous antigens (ones not from the cell itself) to trigger an adaptive immune response by activating cytotoxic CD8+ T cells recognizing the exogenous antigens on the MHC class I complexes.

16. Cross presentation in MHC Molecules

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