18.2 Major Histocompatibility Complexes and Antigen-Presenting Cells
3 min read•june 18, 2024
are key players in our immune system. They're like tiny flags on cells that show what's going on inside. are on all cells, while are on special immune cells.
These molecules help our body recognize and fight off invaders. They work with different immune cells, like T cells, to start an immune response. Understanding MHC is crucial for grasping how our body defends itself against diseases.
Major Histocompatibility Complexes (MHC)
Structure and expression of MHC molecules
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- molecules
- Heterodimers composed of a polymorphic α chain and a non-polymorphic (light chain)
- Expressed on the surface of all (somatic cells and leukocytes)
- Present intracellular antigens such as viral proteins (influenza) and tumor antigens (melanoma) to to initiate cytotoxic immune responses
- Contain a that accommodates antigenic peptides
- molecules
- Heterodimers consisting of polymorphic α and β chains that form a peptide-binding cleft
- Expressed on professional including , , and
- Present extracellular antigens like bacterial proteins (lipopolysaccharides) to to stimulate helper T cell responses and antibody production
Key antigen-presenting cells
- (DCs)
- Most potent APCs with the unique ability to activate naive T cells and initiate primary immune responses
- specialize in antigen uptake, processing, and presentation to T cells in lymph nodes
- Plasmacytoid DCs produce large amounts of ( and ) in response to viral infections (influenza, HIV)
- Capable of , presenting exogenous antigens on MHC I molecules to CD8+ T cells
-
- Phagocytose and degrade pathogens (bacteria, fungi) and present antigens to T cells to stimulate adaptive immunity
- Secrete cytokines (, ) and chemokines to modulate immune responses and recruit other immune cells
- Involved in tissue repair (wound healing) and maintaining homeostasis by clearing apoptotic cells
-
- Primary function involves producing antibodies () to neutralize pathogens and toxins
- Act as APCs by presenting antigens to T cells via MHC II and receiving co-stimulatory signals ( interaction) for activation and differentiation into
Antigen Processing and Presentation
MHC I vs MHC II pathways
- MHC I pathway
- Processes intracellular antigens such as viral proteins (influenza nucleoprotein) and tumor antigens (mutated p53)
- Antigens are degraded by the in the cytosol into peptide fragments
- Peptide fragments are transported into the by the
- Peptides bind to MHC I molecules in the ER lumen and the stable MHC I-peptide complex is transported to the cell surface
- MHC I-peptide complexes are recognized by CD8+ T cells to initiate responses
- MHC II pathway
- Processes extracellular antigens such as bacterial proteins (tetanus toxoid) and allergens (pollen)
- Antigens are endocytosed by APCs and degraded in endosomes/lysosomes by proteases ()
- MHC II molecules are synthesized in the ER and transported to the endosomal compartment
- Peptide fragments bind to MHC II molecules in the endosome and the stable MHC II-peptide complex is transported to the cell surface
- MHC II-peptide complexes are recognized by CD4+ T cells to stimulate helper T cell responses (, ) and antibody production by B cells
- The protects the peptide-binding groove of MHC II molecules during transport from the ER to endosomes
Genetic basis and diversity
- MHC molecules are encoded by in humans, which are highly polymorphic
- This genetic diversity allows for recognition of a wide range of antigens and contributes to individual differences in immune responses
T cell recognition
- T cell receptors (TCRs) on T cells recognize and bind to specific MHC-peptide complexes on APCs
- This interaction is crucial for initiating and regulating adaptive immune responses
Key Terms to Review (61)
Activated macrophages: Activated macrophages are immune cells that have been stimulated by cytokines to enhance their phagocytic, antimicrobial, and antigen-presenting capabilities. These cells play a critical role in the body's defense mechanisms against pathogens and in inflammatory responses.
Activation of B cells: Activation of B cells is the process by which B lymphocytes recognize an antigen, leading to their proliferation and differentiation into plasma cells that produce antibodies. This activation is crucial for the humoral immune response.
Antigen Processing: Antigen processing is the series of cellular events that prepare antigenic molecules, such as proteins or peptides, for presentation to the immune system. This process is crucial for the activation of the adaptive immune response, as it allows the body to recognize and respond to foreign or abnormal substances that could pose a threat.
Antigen-presenting cells (APCs): Antigen-presenting cells (APCs) are immune cells that process and present antigens to T-cells, initiating an adaptive immune response. They play a crucial role in bridging innate and adaptive immunity.
Antigen-Presenting Cells (APCs): Antigen-presenting cells (APCs) are a diverse group of immune cells that play a crucial role in initiating and regulating the adaptive immune response. These specialized cells are responsible for capturing, processing, and presenting antigenic peptides to T lymphocytes, triggering their activation and subsequent immune reactions.
B cells: B cells are a type of white blood cell that plays a crucial role in the adaptive immune system by producing antibodies. They originate in the bone marrow and are responsible for humoral immunity.
B Cells: B cells, also known as B lymphocytes, are a type of white blood cell that play a crucial role in the adaptive immune response. They are responsible for the production of antibodies, which recognize and bind to specific foreign antigens, neutralizing them or marking them for destruction by other immune cells.
Cathepsins: Cathepsins are a family of proteolytic enzymes found primarily within the lysosomes of cells. They play a crucial role in the breakdown and recycling of proteins, as well as in various cellular processes related to immune function and antigen presentation.
CD4 T cells: CD4 T cells are a type of white blood cell that play a crucial role in the immune system by helping to coordinate the body's response to infections. They are also known as helper T cells and are essential in fighting off both viral and bacterial infections.
CD4+ T cells: CD4+ T cells, also known as helper T cells, are a type of lymphocyte that plays a crucial role in the adaptive immune response. These cells express the CD4 co-receptor on their surface, which helps them recognize and respond to antigens presented by major histocompatibility complex (MHC) class II molecules on the surface of antigen-presenting cells.
CD40-CD40L: CD40-CD40L is a critical co-stimulatory interaction that occurs between antigen-presenting cells (APCs) and T cells, playing a crucial role in the activation and regulation of the immune response. CD40 is a cell surface receptor expressed on APCs, while CD40L (also known as CD154) is a ligand primarily found on activated T cells.
CD8+ T cells: CD8+ T cells, also known as cytotoxic T cells, are a subset of T lymphocytes that play a crucial role in the adaptive immune response by directly killing infected or cancerous cells. They recognize antigens presented by major histocompatibility complex (MHC) class I molecules on the surface of target cells and initiate a cytotoxic response to eliminate these threats.
Complement: The complement system is a group of proteins in the blood that aids antibodies and phagocytic cells in clearing pathogens from an organism. It plays a crucial role in both innate and adaptive immunity.
Cross-presentation: Cross-presentation is a process where antigen-presenting cells (APCs) present extracellular antigens via MHC class I molecules to CD8+ T cells. This mechanism is crucial for initiating immune responses against pathogens that do not infect APCs directly.
Cross-presentation: Cross-presentation is a process in which antigen-presenting cells, such as dendritic cells, can present exogenous antigens on their own major histocompatibility complex (MHC) class I molecules, allowing for the activation of CD8+ T cells and the initiation of a cytotoxic immune response against the presented antigens.
Cytotoxic T Lymphocyte (CTL): Cytotoxic T lymphocytes, also known as CD8+ T cells, are a specialized subset of T cells that play a crucial role in the adaptive immune response by directly killing infected or cancerous cells. They are a key component in the major histocompatibility complex (MHC) and antigen-presenting cell (APC) pathways.
Dendritic cells: Dendritic cells are specialized antigen-presenting cells that play a crucial role in the initiation of the immune response. They capture, process, and present antigens to T cells, thereby bridging innate and adaptive immunity.
Dendritic Cells: Dendritic cells are a type of antigen-presenting cell that play a crucial role in the immune system. They act as sentinels, constantly surveying the body for signs of infection or disease, and are responsible for initiating and shaping the adaptive immune response.
Endoplasmic Reticulum (ER): The endoplasmic reticulum (ER) is a complex network of interconnected membranous tubules and sacs within the cytoplasm of eukaryotic cells. It serves as a crucial organelle responsible for various cellular processes, including protein synthesis, folding, and trafficking, as well as lipid and carbohydrate metabolism.
HLA Genes: HLA (Human Leukocyte Antigen) genes are a group of genes that encode major histocompatibility complex (MHC) proteins, which play a crucial role in the immune system's ability to recognize and respond to foreign substances, including pathogens and transplanted tissues. These genes are essential for understanding the concepts of major histocompatibility complexes and antigen-presenting cells.
Human leukocyte antigen (HLA) genes: Human leukocyte antigen (HLA) genes encode for proteins that are essential for the immune system's ability to recognize foreign molecules. These genes are part of the major histocompatibility complex (MHC) in humans.
IFN-α: IFN-α, or interferon-alpha, is a type of cytokine that is produced by various cells, including plasmacytoid dendritic cells and infected cells, in response to viral infections or other stimuli. It plays a crucial role in the body's innate immune response, helping to control the spread of viruses and regulate the adaptive immune response.
IFN-β: IFN-β, or Interferon-beta, is a type I interferon that plays a crucial role in the immune response against viral infections and in the regulation of antigen presentation by major histocompatibility complex (MHC) molecules. It is a signaling protein produced by host cells in response to the presence of pathogens, and it helps coordinate the body's defenses against invading microorganisms.
IL-1: IL-1, or Interleukin-1, is a pro-inflammatory cytokine that plays a crucial role in the immune response and inflammation. It is produced by various cell types, including macrophages, dendritic cells, and epithelial cells, and acts as a key mediator in the activation of the immune system.
Immunodominant: An immunodominant epitope is the part of an antigen that is most effectively recognized by the immune system, eliciting the strongest immune response. These epitopes are crucial in determining the specificity and efficacy of T-cell responses.
Immunoglobulins: Immunoglobulins are specialized glycoproteins produced by B cells that function as antibodies in the immune response. They play a critical role in identifying and neutralizing pathogens such as bacteria and viruses.
Immunoglobulins: Immunoglobulins, also known as antibodies, are glycoprotein molecules produced by plasma B cells that recognize and bind to specific antigens, initiating an immune response. They play a crucial role in the humoral immune system and are involved in various immunological processes described in the topics of 18.2 Major Histocompatibility Complexes and Antigen-Presenting Cells, 18.4 B Lymphocytes and Humoral Immunity, 19.4 Immunodeficiency, and 20.5 Fluorescent Antibody Techniques.
Invariant Chain: The invariant chain is a protein that plays a crucial role in the assembly and trafficking of major histocompatibility complex (MHC) class II molecules. It is essential for the proper functioning of antigen-presenting cells in the immune system.
Macrophages: Macrophages are large phagocytic cells derived from monocytes that play a crucial role in both innate and adaptive immunity. They engulf and digest pathogens, dead cells, and cellular debris.
Macrophages: Macrophages are a type of large white blood cell that play a crucial role in the immune system's cellular defenses, inflammation and fever response, antigen presentation, and defense against bacterial infections. They are derived from monocytes and act as the first line of defense against pathogens and damaged cells.
Major histocompatibility complex (MHC): Major Histocompatibility Complex (MHC) proteins are essential for the immune system to recognize foreign molecules. They play a critical role in antigen presentation to T cells.
Major Histocompatibility Complexes (MHC): Major Histocompatibility Complexes (MHC) are a group of genes that encode cell surface proteins responsible for the recognition of self and non-self molecules, playing a crucial role in the immune system's ability to distinguish between the body's own cells and foreign invaders.
MHC I: MHC I (Major Histocompatibility Complex Class I) molecules are cell surface proteins essential for the immune system to recognize infected or abnormal cells. They present endogenous antigens to cytotoxic T lymphocytes, initiating an immune response.
MHC I Molecules: MHC I molecules, also known as major histocompatibility complex class I molecules, are cell surface proteins that play a crucial role in the immune system's ability to recognize and respond to foreign or abnormal cells. These molecules are responsible for presenting peptide fragments derived from intracellular proteins to cytotoxic T cells, enabling the detection and elimination of infected or cancerous cells.
MHC II: MHC II (Major Histocompatibility Complex class II) are proteins found on the surface of certain immune cells that present antigens to T-helper cells. They play a crucial role in initiating the immune response by displaying foreign peptides to T cells.
MHC II Molecules: MHC II molecules, also known as major histocompatibility complex class II, are specialized proteins found on the surface of antigen-presenting cells. These molecules play a crucial role in the adaptive immune response by presenting peptide antigens to CD4+ T cells, initiating an immune reaction against foreign or harmful substances in the body.
Myeloid DCs: Myeloid dendritic cells (myeloid DCs) are a subset of dendritic cells that originate from myeloid progenitor cells. They are professional antigen-presenting cells that play a crucial role in initiating and regulating immune responses by processing and presenting antigens to T cells.
Natural killer (NK) cells: Natural Killer (NK) cells are a type of lymphocyte that play a crucial role in the innate immune system. They are capable of recognizing and destroying infected or cancerous cells without prior sensitization to antigens.
Nucleated cells: Nucleated cells contain a nucleus and are involved in various cellular processes, including the immune response. They present antigens via Major Histocompatibility Complex (MHC) molecules to T-cells.
PAMPs: Pathogen-associated molecular patterns (PAMPs) are molecular structures found on pathogens that are recognized by the innate immune system. These patterns trigger an immune response aimed at eliminating the pathogen.
Peptide-Binding Groove: The peptide-binding groove is a structural feature found in major histocompatibility complex (MHC) proteins, which play a crucial role in the presentation of antigenic peptides to T cells, a key step in the adaptive immune response. This groove serves as the binding site for short peptide fragments derived from the degradation of foreign or self-proteins, allowing the MHC to display these peptides on the cell surface for recognition by T cell receptors.
Phagocytes: Phagocytes are immune cells that engulf and digest pathogens, cellular debris, and foreign particles. They play a crucial role in both innate and adaptive immunity.
Phagosome: A phagosome is a vesicle formed around a particle engulfed by a phagocyte via phagocytosis. It eventually fuses with lysosomes to digest the ingested material.
Plasma cells: Plasma cells are differentiated B lymphocytes that produce and secrete large quantities of antibodies. They play a critical role in the humoral immune response by targeting specific antigens.
Plasma Cells: Plasma cells are terminally differentiated B lymphocytes that are responsible for the production and secretion of antibodies, playing a crucial role in the humoral immune response. These specialized cells arise from activated B cells and are central to the adaptive immune system's ability to provide long-lasting protection against pathogens.
Plasmacytoid Dendritic Cells (pDCs): Plasmacytoid dendritic cells (pDCs) are a specialized subset of dendritic cells that play a crucial role in the innate immune response, particularly in the recognition and response to viral infections. They are characterized by their unique morphology and their ability to rapidly produce large amounts of type I interferons, which are potent antiviral cytokines.
Plasmacytoid DCs are closely connected to the topics of Major Histocompatibility Complexes and Antigen-Presenting Cells, as they are a specialized type of antigen-presenting cell that can present viral antigens to T cells and initiate adaptive immune responses.
Proteasome: The proteasome is a large protein complex found in the cytoplasm and nucleus of eukaryotic cells that is responsible for the degradation and recycling of unwanted or damaged proteins. It plays a crucial role in regulating protein levels and maintaining cellular homeostasis.
Proteasomes: Proteasomes are protein complexes that degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks peptide bonds. They play a critical role in processing antigens for presentation on MHC class I molecules.
Red blood cells: Red blood cells (RBCs), also known as erythrocytes, are the most common type of blood cell and are responsible for transporting oxygen from the lungs to tissues and carbon dioxide from tissues to the lungs. They lack a nucleus and organelles, allowing more room for hemoglobin, the protein that binds oxygen.
Self-antigen epitopes: Self-antigen epitopes are fragments of proteins or other molecules from an individual's own cells that are presented by major histocompatibility complex (MHC) molecules. They play a crucial role in the immune system's ability to distinguish between self and non-self.
Self-antigens: Self-antigens are molecules or molecular structures naturally present within an individual's own body that are recognized by the immune system. They play a crucial role in distinguishing self from non-self, preventing autoimmune responses.
T cell receptor (TCR): The T cell receptor (TCR) is a complex of membrane-bound proteins expressed on the surface of T cells that recognizes and binds to specific antigenic peptides presented by major histocompatibility complex (MHC) molecules on antigen-presenting cells. This interaction is crucial for the activation and function of T cells in the adaptive immune response.
Th1: Th1 cells are a subset of T helper cells that play a crucial role in cell-mediated immunity and the body's defense against intracellular pathogens. They are responsible for activating and coordinating various immune responses, including the activation of macrophages and cytotoxic T cells.
TH1 cells: TH1 cells are a subset of T helper cells that produce cytokines, primarily interferon-gamma (IFN-γ), to activate macrophages and promote cell-mediated immune responses. They play a crucial role in defending against intracellular pathogens like viruses and certain bacteria.
Th2: Th2 cells, also known as type 2 helper T cells, are a subset of CD4+ T cells that play a crucial role in the adaptive immune response, particularly in the context of allergic and parasitic infections. These cells are responsible for coordinating and orchestrating various immune functions to combat specific types of pathogens and manage inflammatory responses.
TH2 cells: TH2 cells, also known as T-helper 2 cells, are a subset of CD4+ T cells that play a crucial role in humoral immunity by promoting B cell activation and antibody production. They primarily secrete cytokines like IL-4, IL-5, IL-10, and IL-13.
TNF-α: TNF-α, or Tumor Necrosis Factor-alpha, is a pro-inflammatory cytokine produced primarily by activated macrophages and other immune cells. It plays a crucial role in the regulation of immune responses, inflammation, and cell death.
Transporter Associated with Antigen Processing (TAP): The transporter associated with antigen processing (TAP) is a key component in the major histocompatibility complex (MHC) class I antigen presentation pathway. It is responsible for transporting peptides from the cytosol into the endoplasmic reticulum (ER), where they can be loaded onto MHC class I molecules for display on the cell surface and recognition by cytotoxic T cells.
Type I Interferons: Type I interferons are a class of signaling proteins produced by host cells in response to the presence of pathogens, such as viruses, bacteria, and other infectious agents. They play a crucial role in the innate immune response by triggering a cascade of events that inhibit viral replication and promote the destruction of infected cells.
β2 microglobulin: β2 microglobulin is a component of MHC class I molecules, which are crucial for the presentation of endogenous antigens to cytotoxic T cells. It plays a key role in immune surveillance.
β2-microglobulin: β2-microglobulin is a small protein that is found on the surface of most cells in the human body. It is a critical component of the major histocompatibility complex (MHC) class I molecules, which are responsible for presenting antigens to T cells, initiating an immune response. β2-microglobulin also plays a key role in antigen-presenting cells, such as dendritic cells and macrophages, which are essential for effective antigen presentation and immune activation.