Major Histocompatibility Complex Overview

Major Histocompatibility Complex (MHC) and Antigen Presentation

• MHC is a group of genes that code for proteins, crucial for the immune system's ability to recognize and respond to foreign substances.
• The MHC proteins are crucial for antigen presentation, a process where cells display fragments of foreign substances on their surface to T cells.
• The process of antigen presentation involves the binding of antigens to MHC molecules, creating a complex recognised by T cells.
• George Snell, in the 1940s, identified genes essential for transplant tissue rejection in mice, thus initiating MHC research.
• MHC class I presents antigens processed from intracellular proteins to CD8+ T cells (cytotoxic T lymphocytes).
• MHC class II presents antigens processed from extracellular proteins to CD4+ T cells (helper T cells).
• MHC genes are located on chromosome 6's short arm, and are called HLA (Human Leukocyte Antigen) in humans.
• MHC genes are polygenic (multiple genes) and codominant (both alleles from each parent are expressed).
• High polymorphism (variation in MHC genes) is a key factor in immune response diversity.
• MHC genes demonstrate linkage disequilibrium (the tendency for certain alleles to occur together more frequently than expected by chance).

Antigen Recognition by Receptors

• T cell receptors (TCR) bind MHC-antigen complexes on antigen-presenting cells (APCs).
• Antibodies (immunoglobulins) recognise antigens directly.
• Both TCR and antibodies trigger intracellular signal transduction pathways.

T Cell Recognition by MHC

• T cell receptor binding to the peptide residue of MHC is crucial for T-cell activation.
• The shape and structure of MHC molecules determine which peptides they bind.
• Polymorphic residues of MHC form 'pockets' that are specific to certain peptide.

Discovery of MHC Genes

• Initial studies focused on transplant tissue rejection.
• Scientists used immunization and implantation methods to determine specific genes crucial for the response to transplanted cells.
• The crucial genes were found in mice as those genes determine which cells are allowed in the body and recognised as self and non-self.

Different Types of MHC

• MHC class I, presents antigens from intracellular proteins to CD8+ T cells.
• MHC class II, presents antigens from extracellular proteins to CD4+ T cells.

MHC Class I Structure

• MHC class I molecules consist of an alpha chain and a beta-2 microglobulin chain.
• These chains form a groove that binds with peptides derived from intracellular pathogens.

MHC Class II Structure

• MHC class II molecules consist of an alpha and beta chain.
• Peptides are loaded into the groove of the composed chains to be presented to CD4+ T cells for activation and response.

Characteristics of MHC Genes

• MHC genes are on chromosome 6's short arm (HLA).
• They are polygenic, with multiple genes acting together in antigen presentation.
• MHC genes are codominant; alleles inherited from both parents are expressed.
• They exhibit high polymorphism (genetic variations).
• They show linkage disequilibrium, meaning certain alleles tend to be inherited together.

Inheritance of MHC Genes

• MHC genes are inherited in a pattern that affects the genetic diversity of HLA alleles in the MHC gene complex from parents to offspring.

Expression of MHC Genes

• MHC class I is present on all nucleated cells, presenting self and non-self intracellular proteins.
• MHC class II is found predominantly on antigen-presenting cells (APCs), presenting extracellular antigens.

Processing of Antigens and Presentation to T Lymphocytes

• Antigen uptake, processing, and presentation mechanisms differ for MHC class I and II.
• Proteins marked for degradation are directed via proteasomes to be processed into peptides.
• MHC-peptide complexes enter the cell surface for recognition by T cells for appropriate responses.

Antigen Processing and Presentation to CD8+ T Lymphocytes

• Production of proteins in the cytosol; viral proteins enter the cytosol for processing.
• Proteolytic degradation of proteins (for example, viral proteins) into peptides.
• Transport of peptides to the endoplasmic reticulum (ER).
• Assembly of peptide-MHC class I complexes.
• Surface expression of peptide-MHC class I complexes.

Cartoon of MHC Class I Presentation

• Visualization of protein uptake and processing in antigen presentation to CD8+ T cells.
• Proteasome breaks down proteins for peptide formation.
• MHC Class I molecule binds to peptide for presentation.
• CD8+ T cell recognises the complex and activates the cytotoxic response.

Antigen Processing and Presentation to CD4+ T Lymphocytes

• Uptake of extracellular proteins by APCs.
• Processing of internalized proteins within endosomal/lysosomal vesicles.
• Biosynthesis and transport of MHC class II molecules to endosomes.
• Association of processed peptides with MHC class II molecules.
• Expression of peptide-MHC class II complexes.

Comparison between MHC I and MHC II Pathways

• Key differences in processing, presentation, types of antigens, and cell types involved in the two pathways (MHC class I and II).
• Each pathway involves a unique set of enzymes, pathways, and mechanisms.

Functions of Professional Antigen-Presenting Cells

• APCs, such as dendritic cells, macrophages, and B cells, present antigens to T cells, initiating an adaptive immune response.
• They capture, process, and present antigens in distinct ways.
• Presentation of antigens to T cells leads to specific T cell activation, and initiation of downstream immune response.

Costimulatory Molecules

• Costimulatory molecules, such as CD28 and CTLA-4, are essential for full T-cell activation.
• In the absence of co-stimulation, activation of T cells is impeded.

Explore the essential role of Major Histocompatibility Complex (MHC) in the immune system. This quiz covers antigen presentation, the types of MHC molecules, and significant historical contributions to MHC research. Test your knowledge on how MHC proteins interact with T cells to facilitate immune responses.