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What is the role of MHC class I molecules?
What is the role of MHC class I molecules?
MHC class I molecules transmit a signal regarding the presence of infected cells to CD8+ T cells, leading to the destruction of infected cells.
What is the general structure of HLA-class I molecules?
What is the general structure of HLA-class I molecules?
HLA-class I molecules consist of a transmembrane polymorphic 'heavy' chain and a smaller polypeptide called beta-2 microglobulin.
How many HLA-class I molecules can be expressed on cells from genetically unrelated parents?
How many HLA-class I molecules can be expressed on cells from genetically unrelated parents?
Each cell has the potential to express 6 different class I HLA molecules.
Which HLA allele is expressed in most patients with Ankylosing Spondylitis?
Which HLA allele is expressed in most patients with Ankylosing Spondylitis?
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Which HLA genes are expressed in mice?
Which HLA genes are expressed in mice?
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Why are nucleated cells with 'self-peptides' not destroyed by cytotoxic T cells?
Why are nucleated cells with 'self-peptides' not destroyed by cytotoxic T cells?
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How is the antigen eventually presented on the surface of a cell?
How is the antigen eventually presented on the surface of a cell?
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What is cross-presentation?
What is cross-presentation?
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How does Herpes simplex virus affect MHC class I?
How does Herpes simplex virus affect MHC class I?
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How does the Epstein Barr virus affect MHC class I?
How does the Epstein Barr virus affect MHC class I?
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How does cytomegalovirus affect MHC class I?
How does cytomegalovirus affect MHC class I?
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What is MHC class I restriction?
What is MHC class I restriction?
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What are CD1 molecules?
What are CD1 molecules?
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Study Notes
Major Histocompatibility Complex Class I
- MHC class I molecules are cell surface glycoproteins that communicate the presence of infected cells to CD8+ T cells, leading to the destruction of these infected cells.
- Target cells present antigen peptides to CD8+ T cells, with all nucleated cells expressing class I MHC.
- Three classes of MHC molecules include HLA-A, HLA-B, and HLA-C, which exhibit codominance in expression.
Structure of HLA-Class I Molecules
- HLA-class I molecules have a transmembrane polymorphic polypeptide "heavy" chain (approximately 45 kDa) non-covalently associated with β2-microglobulin (about 12 kDa).
- Beta2-microglobulin is non-polymorphic, does not contain a transmembrane domain, and is encoded on chromosome 15, as opposed to the class I MHC which is on chromosome 6.
- Proper folding of the class I MHC 45 kDa chain requires the presence of beta2-microglobulin.
Expression of HLA-Class I Molecules
- If parents are genetically unrelated, each cell can potentially express six different class I HLA molecules due to codominant expression of HLA A, B, and C (one inherited from each parent).
Disease Association
- HLA-B27 is commonly expressed in patients with Ankylosing Spondylitis.
MHC Genes in Mice
- In mice, MHC class I molecules expressed include H2-K, H2-D, and H2-L.
Self-Peptides and Immune Tolerance
- All nucleated cells express HLA-class I molecules loaded with "self-peptides" in the absence of infection, preventing destruction by cytotoxic T cells as the immune system recognizes them as normal.
Antigen Presentation Mechanism
- Microorganisms enter the cytoplasm and are marked by ubiquitin before proteasomal degradation into peptide fragments.
- These fragments bind transport proteins (TAP) and are brought to the endoplasmic reticulum (ER) where they associate with class I MHC molecules before being transported to the cell surface.
Cross-Presentation and Cross-Priming
- Cross-presentation occurs when exogenous antigens are processed differently, not within the phagolysosome, allowing presentation via MHC class I.
- Activation of CD8+ T cells through cross-presentation is termed cross-priming, which can occur if an antigen escapes the endosome and is processed further in the cytoplasm.
Virus Interference with MHC Class I
- The Herpes Simplex Virus (HSV) hinders MHC class I function by producing a protein that prevents peptide transit into the ER, reducing cell surface MHC molecules.
- Epstein Barr Virus (EBV), responsible for mono, inhibits proteosome activity leading to reduced availability of peptide fragments for MHC class I presentation.
- Cytomegalovirus (CMV) represses the display of the antigen peptide/class I MHC complex on cell membranes. It diverts newly formed class I MHC molecules back into the cytoplasm for degradation.
MHC Class I Restriction
- CD8+ T cells exclusively recognize virally infected cells displaying antigenic peptides along with class I MHC molecules, illustrating MHC class I restriction.
CD1 Molecules
- CD1 molecules are glycoproteins that present lipid and glycolipid antigens to specific T cell subsets, structurally resembling class I MHC with β2-microglobulin association.
- Processing and presentation of CD1-antigen complexes are akin to Class II MHC mechanisms, with five CD1 family members divided into two groups: CD1a, CD1b, CD1c, and CD1e as one group, while CD1d forms a distinct group.
- Dendritic cells express all CD1 variants, which possess hydrophobic amino acids that allow interaction with lipid molecules.
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Description
Explore the essential aspects of MHC class I molecules, including their role in immune responses and cell expression. This quiz will delve into properties, nomenclature, and the interaction with CD8+ T cells. Perfect for students studying immunology or related fields.
