Chapter 7: Major Histocompatibility Complex Flashcards
What are MHC proteins?
Membrane-bound surface proteins found on antigen presenting cells that are important for tissue recognition. In humans they are referred to as HLA (human leukocyte antigens)
What are the three classes of MHC genes?
Class 1 and 2 encode glycoproteins.
Class 1 are expressed on all nucleated cells (not erythrocytes)
Class 2 are expressed on antigen presenting cells (macrophages, B-cells, dendritic cells) and occasionally thymic epithelial cells, endothelial cells etc. if induced (by interferon-y)
Class 3 encodes products involved in complement and inflammation, but not covered in this unit.
Define haplotype
Set of alleles for a given gene. In MHC molecules, each haplotype is given a number (HLA A2 B5, meaning you have an A and a B allele for that gene). Most of the population is heterozygous which generates a lot of immunologic diversity (but hard for transplants). These genes are codominant (both are expressed)
What does it mean to be highly polymorphic?
Meaning there are many many different allelic variants
What is the basic structure of MHC Class 1 molecules?
Two non-symmetrical/ uneven chains: a trans-membrane a-chain (a1 and a2 are variable and form a binding cleft, a3 is not variable and contains binding site for CD8+ coreceptor
A B-micro-globulin Which just “hovers” next to the a3 domain near the membrane
—> Binds 8-10 amino acid peptide fragments from an antigen
—> found on all nucleated cells
MHC class 2 structure
Two largely symmetrical chains: a1 and B1 are variable/ polymorphic and contain the binding groove. A2 and b2 are nonpolymorphic and contain the binding site for CD4+ T-cells
—>binds peptides between 13-18 amino acids long
—> Found on antigen-presenting cells (occasionally thymus)
How are the genes for the MHC molecule expressed?
Alleles are codominant and expressed simultaneously
What type of molecules (where they originate) do each class of MHC present
- Class 1 presents intracellular (endogenous) antigen peptides, as well as self-proteins. Activates cytotoxic T-cells
- Class 2 presents extracellular (exogenous) antigen peptides display to and activate helper T-cells
What part of MHC binds CD4 or CD8? Where are these co-receptors found?
- On MHC1, a3 domain binds CD8+ cytotoxic T-cell coreceptor
- On MHC2 a2 AND B2 contain site to bind CD4+ helper T-cell coreceptor
Why is it important to be able to express many different MHC proteins?
It gives the best chance for an organism to have SOME ability of presenting alL the possible antigen peptides it encounters. Also allows presentation of both extracellular (class 2) and intracellular (class 1) antigens
What type of cells present class 1?
All nucleated cells
What types of cells express MHC class 2?
Antigen presenting cells (macrophages, B-cells and dendritic cells)
What is required for a MHC molecule to become stable (resistant to proteolysis)?
Stable expression requires peptide cargo (peptide antigen is linked to MHC during the MHC assembly inside the cell). If not linked, will be degraded.
What are the types of antigen presenting cells? What is their “professional” status and what types of cells do they present to?
- Dendritic cells (professional APC) present to naïve T-cells and cause them to undergo clonal expansion/ differentiation
- Macrophages, present to differentiated effector T-cells
- B-cells present to differentiated helper T-cells
- All nucleated cells can present from intracellular microbes or cancer to cytotoxic T-cells that are already differentiated
What is the function of antigen presenting cells?
- capture antigens
- take them to the correct site (secondary lymphoid organs)
- display antigens so they can be recognized by lymphocytes
- provide second signals for T-cell activation (signal 2= expression of costimulators and secretion of cytokines by APC)