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These comprehensive tertiary-level lecture notes by Dr Samuel Munjita provide an in-depth examination of Major Histocompatibility Complex molecules, a foundational topic for students pursuing degrees or diplomas in immunology, biomedical sciences, or medicine. The material explains the origin, mechanisms of action, and functions of MHC class I and class II molecules, highlighting their critical role in antigen presentation and T cell activation. The notes clearly differentiate between the two classes: MHC I molecules, present on nearly all nucleated cells, present endogenous antigens (like viral proteins) to cytotoxic T lymphocytes (CD8+ T cells), while MHC II molecules, found on specialised antigen-presenting cells like macrophages, dendritic cells, and B cells, present exogenous antigens to helper T lymphocytes (CD4+ T cells). The lecture covers the structure of MHC molecules, detailing the alpha and beta chains, and explains how their flexible binding pockets allow them to present a diverse array of peptides. It also connects MHC function to immune surveillance, graft rejection, autoimmune disorders, and the coordinated activation of T cells through TCR binding and B7-CD28 co-stimulation. This structured content is ideal for university students seeking to master complex immunological concepts for exams, offering clear comparisons and clinical correlations. Download these notes to enhance your understanding of antigen processing and presentation for academic success in tertiary immunology courses.
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Major Histocompatibility molecules Dr Samuel Munjita Lecture objectives At the conclusion of this activity, participants will be able to: Explain the meaning of the origin, mechanisms of action and functions of MHC class I and II molecules Differentiate MHC class I molecules from MHC class II molecules Introduction The major histocompatibility complex (MHC), is so named because of its participation in tissue compatibility or graft rejection. Individuals identical for this region (MHC region) can exchange grafts more successfully than those with different MHC combinations. A major role of the MHC is to bind small peptides and to present them to the cell surface where the antigen can be recognised by T cell receptors Introduction MHC proteins have the capacity to bind to several different peptides, which is necessary as there are a vast number of potential peptide targets, and only a limited number of MHC proteins. Furthermore, the different peptides that an MHC protein can bind are often structurally different from one another. This is an unusual property for a protein, and makes MHC molecules very different from other immune system proteins such as antibodies and T cell receptors, both of which show much greater specificity for their targets. Introduction MHC molecules are able to bind to such diverse peptides, because both the MHC binding pocket and the peptides are relatively flexible, the latter because of their small size. In addition, water molecules can fill in the gaps between the MHC molecule and its peptide to improve its fit. MHC molecules: a means of Antigen Processing In humans, the MHC genes encode the human leukocyte antigens (HLAs) on the cell surface. Proteins inside the cell are broken down into short fragments that can be displayed as peptide antigens by MHC molecules on the surface of the cell. MHC molecules display both ‘self’ peptides derived from their own proteins, and foreign peptides derived from invading pathogens. MHC molecules: a means of Antigen Processing The immune system is constantly monitoring the surfaces of cells, and the MHC-presented peptides help immune cells to discriminate between normal antigens on the surface of all cells, and those that are foreign and potentially dangerous. The immune system also monitors the amount of MHC-presented antigens, which helps them to target and destroy cancerous cells that often display increased amounts of self-antigens. Defects in certain MHC genes lead to autoimmune disorders in which the body fails to recognize self-antigens, such as occurs in diseases like multiple sclerosis, inflammatory bowel disease, and in some forms of arthritis and diabetes. Review: Activation of T cells APCs ( e.g. Interdigitating DCs) capture Ag and migrate to the lymphoid tissue where they express higher MHC class II and co-stimulatory molecules such as B7.1 and B7.2. T cell receptor binds MHC-peptide complex B7-CD28 co-stimulation cytokine release NB: CD28 is a T cell receptor which binds B7 and stimulate release of cytokines Classes of MHC molecules There are two major classes of MHC molecules, both of which consist of an α and a β chain, but from different sources. MHC class I molecules (MHC I) consist of one membrane-spanning α chain (heavy chain) produced by MHC genes, and one β chain (light chain or β2-microglobulin) produced by the b2-microglobulin gene. MHC class II molecules (MHC II) consist of two membrane-spanning chains, α and β, of similar size and both produced by MHC genes. Classes of MHC molecules In each case, the MHC molecule has a groove that binds a peptide, which it can then present at the cell surface to a T cell to elicit an immune response. Remember: T cells only recognise antigens as complexes with MHC molecules. The two classes of MHC proteins differ not only in their structure, but more importantly in their functional roles within the immune system: the two types of MHC molecules are specialised to present different types of antigens, thereby eliciting different responses. MHC class I MHC I glycoproteins are present on almost every cell in the body, acting to present endogenous antigens that originate from the cytoplasm. These antigens include not only self-proteins, but also foreign proteins produced within the cell, such as viral proteins that take over the cell’s machinery in order to replicate the …
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