Major Histocompatibility Complex Class I

Questions and Answers

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?

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?

Each cell has the potential to express 6 different class I HLA molecules.

Which HLA allele is expressed in most patients with Ankylosing Spondylitis?

HLA-B27 Signup and view all the answers

Which HLA genes are expressed in mice?

MHC class I molecules are H2-K, H2-D, and H2-L. Signup and view all the answers

Why are nucleated cells with 'self-peptides' not destroyed by cytotoxic T cells?

Infected cells are identified for destruction by CD8+ T cells when they display an antigen fragment in association with class I MHC molecules. Signup and view all the answers

How is the antigen eventually presented on the surface of a cell?

Antigens are processed in the cytoplasm, and peptide fragments bind to class I MHC molecules which are then displayed on the cell surface. Signup and view all the answers

What is cross-presentation?

Cross-presentation is the process where exogenous antigens are presented by class I MHC molecules. Signup and view all the answers

How does Herpes simplex virus affect MHC class I?

HSV produces a protein that inhibits the translocation of peptides into the ER, preventing MHC class I complex formation. Signup and view all the answers

How does the Epstein Barr virus affect MHC class I?

EBV inhibits proteosome activity, preventing the hydrolysis of the virus into peptide fragments. Signup and view all the answers

How does cytomegalovirus affect MHC class I?

CMV inhibits the expression of the antigen peptide/class I MHC complex on cell surfaces. Signup and view all the answers

What is MHC class I restriction?

CH8 + T cells only recognize cells infected with a virus if they display the antigenic peptide in association with class I MHC molecules. Signup and view all the answers

What are CD1 molecules?

CD1 molecules are glycoproteins that present lipid and glycolipid antigens to subsets of T cells. Signup and view all the answers

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.