MHC Flashcards
What are cogenic strains of MHC?
strains in which the endogenous MHC is replaced by an entire MHC locus form another strain
What are recombinant strains of MHC?
strains in which only a portion of the endogenous MHC complex has been relplaced by MHC of another haplotype (breeding from 1 strain into another)
Which cells express MHC I?
all cells in body (except RBCs)
Which cells express MHC II?
APCs (antigen presenting cells): activated T cells, B cells, macrophages, dendritic (other APC), thymic epithelium
NB: neurons do NOT express Class II but brain microglia (of monocyte/macrophage lineage) do express class II
How do T cells recognize viral antigens in virus infected cells?
only as complex with MHC antigens
[For both Cytotoxic T cells and T helper cells: the ability of T cells to recognize a particular MHC as self depends on the MHC haplotype(s) present in the thymus in which they matured]
Which T cells express CD4?
Helper T
Which T cells express CD8?
Cytotoxic T
Which T cell marker is on all T cells?
CD3?
Which MHC class interacts with CD4?
II
Which MHC class interacts with CD8?
I
Single mutations in T cells alter MHC . Which mutation (in B6 mice) alters Class I? Class II?
bm1: Class I
bm12: Class II
Name the MHC class that presnet antigens that originate within the cell. (like viruses and tumor antigens)
MHC Class I
Name the MHC class that present antigens that originate outside the cell.
MHC Class II
Can antigens be presented on both class I and class II MHC?
yes: “cross” pathways
eg: a virus that ends up in endosomes
Result: leads to two different types of immune rxns
How are most bacteria handled?
Most are extracellular:
T cell help –> Ab production –> processed for Class II presentation
TH cells recognize exogenous antigen which is phagocytosed and presented by Class II
How are most viruses handled?
Most are inside cell: require CTL (cytotoxic T cell) to kill infected cell
CTL recognize antigen synthesized inside cell, which is presented by class I
Steps of Class I MHC Presentation
1) Proteosome cleaves antigens into fragments
2) TAP system transports them to lumen of RER
3) Newly made fragments bind to newly-made Class I MHC and get shipped in vesicle to fuse with PM
4) CTL receptor binds Class I MHC + antigen fragment
Steps of Class II MHC Presentation
1) Antigen phagocytosed by APC
2) Proteolytic cleavage within endosome
3) Binding to Class II MHC in endosome
4) export of antigen/MHC complexes to PM
5) TH receptor binds to Class II MHC + antigen fragment
Answer for Class I molecules:
- peptide binding domain?
- nature of peptide-binding cleft? (open/closed)
- size of peptides (# of AAs)
- anchor residue motifs (where on peptide?)
- nature of bound peptide?
- peptide binding domain? alpha 1/alpha2
- nature of peptide-binding cleft? closed at both ends
- size of peptides: 8-10 AAs
- anchor residue motifs: STRONG motifs; anchors at both ends of peptide; generally hydrophobic
- nature of bound peptide? extended structure with both ends interacting with MHC cleft but middle arches up away from MHC
Answer for Class II molecules:
- peptide binding domain?
- nature of peptide-binding cleft? (open/closed)
- size of peptides (# of AAs)
- anchor residue motifs (where on peptide?)
- nature of bound peptide?
- peptide binding domain? alpha 1/BETA1
- nature of peptide-binding cleft? OPEN at both ends
- size of peptides: 13-18 AAs
- anchor residue motifs: WEAK motifs; anchors residues distributed along the length of the peptide
- nature of bound peptide? extended structure that is held at constant elevation above MHC
What is the fate of an antigen-presenting cell with no B7?
anergy of TH cell
What are the two types of CD4+ cells (T helper)
Th1 (inflammatory);
Th2 (helper)
What is the function of Th1 cells?
(inflammatory)
B-cell proliferation; polyclonal Ig secretion; *cytotoxcity; *suppression of Ig secretion; *delayed-type hypersenstivity (DTH)
Note: * means unique to this cell
What is the function of Th2cells?
(Helper)
B-cell proliferation;
polyclonal Ig secretion;
*HELP FOR SPECIFIC Ab!
Note: * means unique to this cell
What cytokines are released from Th1 cells?
(pro-inflammatory)
IL-2,* IL-3; GM-CSF; *IFN-gamma, *TNF-Beta TNF-alpha
Note: * means unique to this cell
What cytokines are released from Th2 cells?
IL-3;
*IL- 4, 5, 6, 10;
GM-CSF;
TNF-alpha
Which cytokines are released from any/all CD4+ cells?
IL3, GM-CSF; TNF-alpha
What is the role of the thymus for T cells?
maturation and selection
What is negative selection of T cells?
Round II of selection:
T cells that recognize self-antigens are not allowed to exit the thymus and are eleminated
Removes Tcells that show dangerously high reactivity to self
What is positive selection of T cells?
Round I of selection:
ONLY cells with TCR that match self with MHC (with at least some affinity) are allowed to mature
Purpose: weed T cells with TCRs that don’t match a self-MHC (bc it is useless)
What is “round III” of selection? (immune response creation)
takes place after T cells mature:
Match self MHC + foreign peptide well?
Y: survive and divide –> create immune response
N: die
the set of foreign antigens encountered determines which immature T cells will make immune responses, proliferate, and give rise to long-lived descendants
Which class of MHC activates the immune system?
MHC II
Which class of MHC responds to virally infected cells?
MHC I
What is TAPASIN?
protein that fxns as bridge btwn TAP and MHC-I in the presentation pathway (MHC-I)
-edits the peptide repertoire, making sure only high affinity peptides are presented
What is ERAP?
MHC-I presentation pathway
ER aminopeptidase: trims peptides in ER prior to binding to MHC class I. Creates peptides that are the correct size
What is the “invariant chain” in the MHC-II pathway?
binds to MHC-II in ER and facilitates transport from ER to endosomes; portion of chain is bond in class II peptide groove
What is DM’s role in the MHC-II pathway?
edits peptide repertoire, making sure only high affinity peptides are presented
What do Myeloid dendritic cells (mDC):
- produce?
- express?
- produce: IL-12
- express: TLR 2, 4
effective in antigen presentation
What do plasmacytoid dendritic cells (mDC):
-express?
express: TLR 7, 9; high levels of IFN-alpha (impt in viral infections)
lymphoid origin?
How are antigens captured?
- passing epithelium of skin, GI tract, resp tract
- lymph node collects antigen from epithelium and CT
- blood borne antigens are captured by APCs in spleen
What (receptors/molecules) do immature dendritic cells produce?
purpose: antigen capture
Express Fc receptors and mannose receptors (help them capture things)
- low expression of T cell activating molecules (B7; ICAM-1; IL-12)
- short half-life of MHC-II molecules
What (receptors/molecules) do mature dendritic cells produce?
(Purpose: antigen presentation to T cells)
-high expression of molecules involved in Tcell activation (B7, ICAM-1, IL-12)
- no expression of Fc receptors or mannose receptors
- longer half life (>100hr)
- 7x amt of surface molecules compared to immature DCs
What is responsible for immature to mature DC conversion?
TLR ligation (when DC eat pathogen and receives TLR ligation
What MHCs do APCs express?
Class I and Class II
How do DCs present antigens, and what’s the response?
*NATIVE T CELL ACTIVATION
Present with costimulator (B7) to CD28 of native T cell to activate the Native T cell toward differentiation to effector T cells and clonal expansion
How do macrophages present antigens, and what’s the response?
EFFECTOR T CELL ACTIVATION (AND activation of macrophages: cell-mediated immunity)
Macrophage presents antigen to Effector T cell which then results in killed microbe
How do B cells present antigens, and what’s the response?
EFFECTOR T CELL ACTIVATION (AND B cell activation and Ab production –> humoral immunity)
B cells present antigen to effector T cells –> Abs
What process allows for viral peptides to be bound to MHC I molecules?
DCs can ingest viral infected cells and display peptides bound to MHC I –> cross presentation provides way for naive CD8 T cells to get activated
What type of peptides are on the majority of class I and class II?
self-peptides (but no reaction bc tolerance has been established; unless autoimmunity)
Where are most of the genes for MHC I and II?
MHC is POLYGENIC (and polymorphic) –> variation
HLA Genetic Region:
Class I: A, B, C
Class II: DP, DQ, DR
Note: genes for invariant chain and Beta2m are on other chromosomes
Where do most of the polymorphisms lie in MHC?
in peptide binding groove
