Major Histocompatability Complex Flashcards
What are the charcateristics of the MHC?
- in all vertebrates
- tightly linked cluster of genes
- self vs non-self
- critical in adaptive immunity
- important for transplantation
What are the 3 genetic regions on chromosome 6?
- MHC Class 1 coded for by A, B, and C alleles
- MHC Class 2 coded for by DR, DQ, and DP
- MHC Class 3 codes for cytokines and complement components
What is syngeneic?
genetically indentical individuals
What is allogeneic?
genetically dissimilar individuals
How are the protein products of chromosome 6 class 1 MHC alleles expressed?
co-dominance
What is the relationship between MHC and T cells?
- T cells DO NOT become stimulated by Ag alone
- Ag must be presented to T cells
- Ag is presented to TCR on T cells
- Ag nestled wihtin MCH on APC is presented on TCR
What do T cells see as altered self?
- allogenic MHC
- allogenic MHC plus self peptide
Where is Class 1 expressed?
- on all nucelated cells
- predominantly on lymphocytes
What is the characteristic of peptide binding in Class 1?
self-peptides found in grooves of MHC
What is the importance of Class 1 HLA antigens?
- presenting endogenous Ags
- cell-mediated immunity -> T cells
What chains make up HLA Class 1?
- alpha: coded for by HLA genes
- beta-2 microglobulin
What chains make up HLA Class 2?
alpha and beta chains
How is the cleft created to hold Ag in Class 1?
alpha 1 and 2 domains fold
Is the beta chain in Class 1 polymorphic or non-polymorphic?
non-polymorphic
Where is Class 2 expressed?
on Ag presenting cells (macrophages, dendritic cells, B cells)
Which chains are highly polymorphic?
aplha and beta chains in MHC Class 2
What is the importance of Class 2?
- presentation of exogenous Ag
- humoral immunity
What class interacts with CD8 (cytotoxic) positive cells?
Class 1
What class interacts with CD4 (helper cell) positive cells?
Class 2
What is the function of CD4 and CD 8?
- CD 4 binds to beta-2 domain of MHC class 2
- CD8 binds to alpha-3 domain of MHC class 1
What are the 2 types of TCR?
- alpha beta
- gamma delta
What leads to signaling?
TCR in combination with CD3 receptor
What is education?
T cells learn to bind to self-MHC
What are the stages of antigen processing and presentation?
- uptake: access to degradation pathways
- degradation: limited proteolysis of Ag to peptides
- Ag-MHC complex formation: peptides loaded onto MHC molecules
- Ag presentation: transport of peptide-MHC complex to surface
What are the characteristics of endogenous antigens?
- within cells as a result of cell metabolism
- within infected cells (ex: viral, intracellular bacteria)
- tumor cells
- associate with MHC Class 1/ CD8 +
What are the characteristics of exogenous antigens?
- taken into Ag-presenting cells
- ex: extracellular bacteria
- processed into fragments
- associate with MHC Class 2/ CD4+
What are the major components of the endogenous pathway?
- Class 1 MHC
- TAP-1 and 2
- proteasome
- tapasin
What are the steps of the endogenous pathway?
- cytoplasmic Ag endogenously processed
- peptides transported by TAP into ER
- MHC Class 1 made in ER
- tapasins attach MHC Class 1 molecules to TAP
- peptides transported into ER by TAP
- peptide MHC complexes transported to cell surface
- MHC/ Ag can interact with CD8+ cells
What are the major components of the exogenous pathway?
- endosomes
- CLIP
- invariant chain (Ii)
What are the steps of the exogenous pathway?
1.protein Ags ingested by APCs (lysosomal vesicles)
2. protein Ags become peptides
3. Class 2 invariant chain is removed
4. DM removes CLIP
5. Class 2 molecules bind peptides from protein
6. peptide Class 2 MHC transported to cell surface
7. interact with CD4 + cells
How does the receptor interact with the golgi in each pathway?
- endo: present with Ag in golgi
- exo: doesn’t receive Ag until it goes through golgi
