The major histocompatibility complex (MHC) is a closely related group of genes whose products are involved in cell-to-cell recognition and self-differentiation. MHCs are present in all mammalian species. MHC is called the HLA complex in humans and the H-2 complex in mice.
MHC genes and functions:
It is a cluster of genes within a large stretch of DNA on chromosome 6 that encodes three classes of molecules
- Klasa I MHCgenes: codes for glycoproteins expressed on the surface of the kidneyall nucleated cells; the primary function of the class I gene product ispresentationof peptide antigens inTC station.
- MHC class II genecodes for glycoproteins expressed primarily inArmored transport vehicles, where they present processed antigenic peptides to TH cells.
- MHC class III genes encode various secreted proteins that have immunological functions, including components of the complement system and molecules involved in inflammation (eg, TNF, heat shock proteins).
MHC class I is found on all nucleated cells. MHC class I mediates immune responses against endogenous antigens. Usually, these MHC class I-expressing cells are infected by virus or tumor cells.
MHC class I represents peptides with a size of 8-10 amino acids, which will then be recognized by cytotoxic T cells.
Structure MHC class I
- chain anchored to the plasma membrane by its hydrophobic transmembrane segment and its hydrophilic cytoplasmic tail
- the chain has 3 outer domains
- Confession between a3& b2microglobulin and constant regions in immunoglobulins
MHC class I-peptide interaction and Presentation
A uninucleate cell expresses105copies of each class I molecule. MHC class I will express many different peptides simultaneously on the surface. Each class I type (A, B, C in humans) binds a unique set of peptides and presents these peptides to CD8+ T cells.
Endogenous therapeutic pathway
- MHC class I molecules bind peptides derived fromendogenous antigensprocessed in the cytoplasm.
- Proteins enter the cytoplasm of cells either by phagocytosed microbes or by endogenous synthesis by microbes such as viruses found in the cytoplasm of infected cells.
- Cytoplasmic proteins are unfolded, ubiquitinated and degraded by proteosomes.
- The protease will cleave the intracellular protein into smaller peptides.
- Peptides will be transported to the endoplasmic reticulum by the TAP transporter, where the peptide binds to newly synthesized MHC class I molecules.
- The8 – 10 amino acidsresidues will bind to MHC class I.
- The MHC class I antigen complex will migrate to the cell surface and ispresented by CD8+ T cells.
- CD8+ T cells can recognize the MHC-I antigen complex and further processing takes place.
MHC class II protein is found on antigen presenting cells (APCs). MHC class II can bind to different peptides and present them to CD4+ T cells. MHC class II mediates immune responses against foreign antigens.
MHC class II will bind to amino acid residues that are 13-18 in size and will be recognized by helper T cells. These cells are phagocytic and can engulf the extracellular antigen.
Structure of MHC II
- Contains 2 different polypeptide chains: β-chain (33 kDa) and β-chain (28 kDa)
- Each chain has 2 outer domains
- Dissociation of antigen binding for processed antigens
- ab heterodimer "dimer dimera".
MHC class II peptide interaction and presentation
MHC class II molecules bind peptides derived from exogenous antigens that are internalized by phagocytosis or endocytosis and processed within the intracellular pathway. APCs can internalize antigens by phagocytosis and/or endocytosis. Macrophages do both. B cells use receptor-mediated endocytosis.
External placement therapy
- Microbial proteins enter the so-called intracellular vesiclesendosomes or phagosomes,which can be merged withlysomere. Internalized antigen is cleaved into peptides.
- APCs synthesize MHC class II molecules in the endoplasmic reticulum (ER).
- Each new compositionMHC-II carries an invariant chain or CLIPwhich binds to the peptide-binding cleft and thus occupies the peptide-binding domain.
- This MHC class II initiates its transport to the cell surface in an extracellular vesicle, which then fuses with an endosomal vesicle containing degraded peptides derived from ingested extracellular proteins.
- The endosomal vesicle containsa protein called DM, which removes CLIP.Therefore,analysis is availableI am doingaccept peptides.
- Internalized antigen takes 1-3 hours to pass through the intracellular pathway and appears on the cell membrane asMHC class II peptides.
- If the MHC II molecule does not find a suitable peptide to bind to,the empty molecule is unstableand is degraded by proteases in endosomes.
- MHC-II will migrate toby phagolysis,which will bind to its components13-18 amino acidsin size.
- Once bound, MHC class II will migrate across the membrane to present the antigen. Ahelper T cells will recognizecomplex and triggers the appropriate response.
The difference between MHC I and MHC II
The main difference between MHC class I and MHC class II (including their antigen processing and presentation pathway) is summarized in this table:
MHC class I MHC class II Structure MHC class I molecules consist of a membrane-spanning α-chain (heavy chain) produced by MHC genes and a β-chain (light chain or β2-microglobulin) produced by the β2-microglobulin gene. MHC class II molecules consist of two membrane-spanning chains, α and β, of similar size and both produced by MHC genes. Types of armored personnel carriers MHC I glycoproteins are present in all nucleated cells. MHC II glycoproteins are present only on specialized antigen-presenting cells (APCs), including macrophages that ingest foreign particles such as bacteria, dendritic cells that present antigen to T cells, and B cells that produce antibodies. The nature of antigen presentation MHC class I glycoproteins represent endogenous antigens derived from the cytoplasm. MHC II proteins represent exogenous antigens derived extracellularly from foreign bodies such as bacteria. Peptide size MHC class I represents peptides of 8-10 amino acids MHC class II represents peptides of 14-18 amino acids. Appropriate T cells Antigen present on cytotoxic T lymphocytes (CD8+ T cells). Antigen present on helper T-lymphocytes. (CD4+ T cells). Responsible co-recipient It binds to CD8 receptor molecules on cytotoxic T cells It binds to CD4 receptor molecules on helper T cells Sources of protein antigens Cytoplasmic proteins (mainly synthesized in the cell, can enter the cytoplasm by the phagosome) Endosomal/lysosomal proteins (mostly internalized from the extracellular environment) Enzymes responsible for creating peptides The cytosolic proteasome Endosomal and lysosomal proteases (e.g. cathepsins) MHC-peptidladningsted Endoplazmatski network A specialized vesicular compartment Molecules involved in peptide transport and loading of MHC molecules Supporters, TAP to ER Officers in the emergency room. invariant chain in ER, Golgi and MHC class II/class II compartment vesicles. DM The end result Presentation of foreign intracellular antigens or altered self-antigens. targeting the station for destruction Presentation of foreign extracellular antigens. it stimulates antibody production and attracts immune system cells to the site of infection
- Development of humoral and cellular immune response
- Antigen recognition by T cells:T cells recognize the antigen only when combined with the MHC molecule
- The T cell receptor (TCR) can only bind to protein-processed peptides, not whole proteins.
- MHC-bound peptides are presented to T cells
- The two major MHC classes important for adaptive T-cell responses are MHC-I and MHC-II. MHC-I presents the peptide to CD8 T cells and MHC-II presents the peptide to CD4 T cells.
- Determining whether the transplanted tissue will be histocompatible or histocompatible
MHC polymorphism and significance
MHC gen vandvery versatile(presence of multiple alleles at a specific genetic locus within a species). The polymorphism is so great that NO two individuals in the normal population of non-bearded animals have exactly the same genes and MHC molecule.
- These polymorphic residues determine which peptides are presented to which MHC molecules
- This evolution of MHC polymorphism ensures that the population will not succumb to a microbe that mutates its proteins, because at least some individuals will be able to mount effective immune responses to the peptide antigens of newly introduced or mutated microbes.
- The MHC expressed in an individual does not change over time, but differs significantly from those expressed by another individual of the same species
- Different combinations of alleles make up that individual's MHC identity
- There are many, many alleles and thousands of combinations, which is why it is so difficult to find someone whose HLA markers match another person, but it is not impossible, there are thousands of transplants every year.
References and further bibliography:
- Cellular and Molecular Immunology, 9. udg
- Kuby Immunology, 8th ed
- Roitt's Essential Immunology, 13. izdanje
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MHC Class I utilizes a proteasome. MHC Class II uses a endolysosome to cut their peptides.What is the function of MHC 1 and MHC 2? ›
Major histocompatibility complex (MHC) class I and class II proteins play a pivotal role in the adaptive branch of the immune system. Both classes of proteins share the task of presenting peptides on the cell surface for recognition by T cells.