MHC Flashcards
What chromosome is the MHC complex on?
Human chromosome 6, mouse chromosome 17
What important T-cell suppressing drug increased the success of tissue transplantation?
Cyclosporine (disc 1969)
What is the MHC gene complex called in mice?
H-2 complex
What is the MHC gene complex called in humans?
HLA complex
What does HLA stand for?
Human leukocyte antigen
MHC is generally inherited as a unit, known as what?
A haplotype
How is MHC inherited?
One haplotype from each parent
What percentage of the MHC gene product is expressed?
All of it; no allelic exclusion
What are the subunits of a class 1 MHC molecule?
α1, α2, α3; β2 microglobulin
Where is the binding groove located on the class 1 MHC?
Between subunits α1 and α2
What length of peptide Ag is bound by class 1 MHC?
8-10 AA
The TCR of the Tc cell binds what on the target cell?
Class 1 MHC molecule α1 and α2 subunits with bound peptide Ag
What does CD8 interact with on the target cell?
Class 1 MHC domains α2, α3, and β2 microglobulin
Which MHC class 1 subunits exhibit the greatest genetic diversity between individuals?
Subunits α1 and α2
What is the gene arrangement of HLA?
Class 2-Class 3-Class 1
Class 2 loci contains what genes?
DP, DQ, and DR
Class 1 loci contains what genes?
B, C, and A
What do the ABC genes of Class 1 encode for?
The α chain
What do Class 2 genes DP, DQ, and DR encode?
Both α β chains
On what cells are class 1 MHC molecules expressed?
Nearly all uncleared cells
What cells exhibit low expression of MHC1?
Hepatocytes
What cells exhibit no expression of MHC1?
Sperm, neurons, and erythrocytes
What cells express MHC2?
APCs: macrophages, dendritic cells, and B cells
Expression of MHC molecules is both _____ and _____.
Coordinate and codominant
What is meant by coordinate expression?
All class 1 or 2 genes are expressed at the same time; ex: a dendritic cell will constitutively express HLA-DP, DQ, and DR molecules on its surface at any given time
What is meant by codominant expression?
Both maternal and paternal haplotype are expressed
Why are MHC genes called polygenic?
Each individual has multiple genes for MHC 1 and 2
What 3 things are required for T cell activation?
Ag processing, Ag presenting, MHC must be self
What molecule is exogenous Ag presented on?
MHC2
What molecule is endogenous Ag presented on?
MHC1
What Ags aren’t presented on MHC molecules?
Non-protein Ags (lipids and glycolipids)
What T cells recognize non-protein Ags?
γδ Τ cells
What are “professional” APCs?
Dendritic cells, macrophages, and B cells
What are “nonprofessional” APCs?
Fibroblasts (skin), vascular endothelial cells, thymic epithelial cells
Where are MHC2 α and β chains synthesized?
Rough endoplasmic reticulum
What roles does the invariant chain play?
Acts as a chaperone to ensure correct folding of chains, acts as a peptide blocker to prevent endogenous peptide from binding, acts as a router to transport the MHC2 to the membrane
After synthesis, where does the MHC2 + invariant chain complex go?
Acidic, peptide containing endosome
Partial digestion of the invariant chain results in only _____ remaining in the MHC2 binding groove
CLIP (class-2 associated invariant chain peptide)
CLIP is exchanged for peptide via what protein?
The chaperone HLA-DM
What are two examples of endogenous peptide Ag?
Viral proteins, mutated cancer proteins
