MHC and Antigen Presentation - Genetic Organization and Structure

Hey there! Just like always, we have got a very interesting immunology video for you on the topic of “MHC and Antigen presentation”. It’s a fascinating but complicated topic to grasp, so in this video, we tried to make things as simple as possible for you to understand. You will get to know! What is MHC? Why is it necessary for Antigen presentation? What pathways are followed for Endogenous and exogenous antigen presentation? And much more. So, let’s have a brief look at our video here! ▬ Major Histocompatibility Complex ▬▬▬▬▬▬▬▬▬▬ MHC stands for Major Histocompatibility complex. MHC is a region of DNA, that encodes a group of molecules that, recognize Antigen. And then make the bond with that antigen and present it to the respective T-cell lymphocytes for further action against that antigen. MHC found in humans is named “Human Leukocyte Antigen (HLA)” and is found in Chromosome # 06. The product of this gene region is then called “MHC molecules or HLA molecules”. These molecules have a specialty in that they can differentiate between self and non-self-cells of the body, and in this way, they play a vital role in Graft rejection by detecting foreign cells. 👉 Genetic organization There are around 224 Loci that have been identified in the HLA region, of chromosome # 06. Genes that encode MHC molecules are the most variable genes known in the human genome. So, It means, MHC follows Genetic polymorphism. Polymorphism refers to the presence of two or more forms of DNA sequences among individuals or populations. In other words, it is said that there are multiple alleles for the same gene. These Loci of MHC are classified into 3 major classes. That is: 🟡 MHC-I 🟡 MHC-II 🟡 MHC-III 👉 Structure of MHC MHC-I and MHC-II molecules are non-covalently associated heterodimers. Both consist of 2 polypeptide chains called alpha and Beta. However, their domains and types of chains involved are different. These molecules have a binding groove, where they get attached to specific antigenic polypeptides. And on the other end, there is a base, that allows them to stand over the surface of nucleated target cells and Antigen presenting cells. 👉 Antigen Processing The major role of MHC molecules is to recognize Exogenous and endogenous antigens and present them over the surface of target cells or Antigen-presenting cells, to the T-lymphocytes of adaptive immunity. But before this presentation, MHC molecules are generated within the endoplasmic reticulum, and the antigens are processed within the cell before their attachment over MHC molecules. So, The process whereby antigen becomes associated with self-MHC molecules for presentation to T cells is called antigen processing. This process is necessary before antigen presentation to T cells, because, unlike B cell receptors, TCRs do not attach directly with the antigen, but they require an MHC-Antigen complex for their recognition of foreign antigen, and so they take further action against that invading pathogen. ▬ Antigen Processing Pathways ▬▬▬▬▬▬▬▬▬▬ There are also two main pathways of Antigen processing. These are: 🟠 Class 1 Pathway/ Endogenous Pathway 🟠 Class 2 Pathway/ Exogenous Pathway 👉 Class 1 pathway Class 1 pathway is specific for Intracellular or endogenous antigens processing. For instance, Peptide antigens generated in the cytosolic compartment of the cell, such as from viruses and bacteria that replicate in the cytosol, bind to class I MHC molecules for presentation to CD8+ T cells by Class 1 pathway. 👉 Class 2 Pathway Class 2 pathway is specific for Extracellular or Exogenous antigen processing. For instance, Peptide antigens generated in endosomes from the endocytic uptake of extracellular antigens, such as toxins, or from microbes captured in endosomes, such as after the phagocytic uptake of certain bacteria by macrophages, bind to class II MHC molecules for presentation to CD4+ T cells. 👉 MHC Restriction MHC binds with antigenic peptides and then presents it to T cells. This MHC-Antigen complex is then recognized by T cells, and this recognition is highly restricted. 👉 The major subsets of T lymphocytes, 🔹the T-helper cells or CD4+ T cells, 🔹and the cytotoxic T lymphocytes 🔹or CD8+ T cells. Both these subsets have different MHC restrictions. ▪️Thus the CD4+ T cell and APC interaction is MHC class II restricted. ▪️The CD8+ T cell and target cell interaction is MHC class I restricted. We have described this MHC restriction of T lymphocytes, by explaining the MHC-Antigen-T cell complex, in this video. So, there’s a blast of knowledge waiting for you. Make sure to watch the video all the way through and remember to explore our other Immunology videos for additional insights.