Lecture #4 Flashcards
Professional APCs are
DC: present Ag for naive T cell and activatng them in the LN Macrophages: present Ag to effector Th1 cells B cells: present Ag to effector Th2 cells
MHC complex in the genome
HLA genes on the short arm of ch6
HLA alleles for MHC I
Classical: A, B, C
Non classical: E, F, G
HLA alleles for MHC II
Classical: DP, DQ, DR
Non classical: DM, DO
MHC I structure
Alpha chain (alpha 1, 2, 3)
Alpha 1 and alpha 2 forming the Ag binding site and alpha 3 forming the TM domain
Beta 2 microglobulin subunit (has no TM domain)
Ag binding site is a closed pocket framed by alpha helicies to fit only 8-9AA
MHC II structure
Alpha and beta globulins with 2 subunits each
Alpha 1 and beta 1 form the Ag binding site, open pocket framed by alpha helicies to fit 10-20AA Ag
Alpha 2 and beta 2 have TM domains
What are the specific AA locations on the Ag that MHC binds?
MHC I bind AA in position 1 and 8/9
MHC II binds AA in position 1, 4, 6, 9
?What is the bond type between an Ag and MHC
H bonds
Expression of MHC and costimulatory molecules by DC
DC in the tissues express very little MHC as oppose to DC in lymphoid organs
Costimulatory molecules are constituitivly expressed
Expression of MHC and costimulatory molecules by macrophages
MHC expression is induced in macrophages from no expression to high expression
so does costimulatory molecules
Expression of MHC and costimulatory molecules by B cells
MHC is contantly expressed at high amount and can be further induced
Costimulatory molecules are induces from zero to high expression
Unprofessional APCs during severe inflammation
Fibroblast in the skin
Glial cells in the brain
Pancreatib beta cells
All nucleated cells express maximum ___ MHC I variations
6
Professional APCs express maximum ___ MHC variations
12
Exibiconism
Continuous expression of self antigens with simultaneous presentation of tumor or viral antigens
Endogenous antigen presentation process
- Endogenous proteins or DRIPs are targeted to proteosomal degradation
- TAP1/2 complex transpor the small peptides to the rER lumen and link them to an MHC I
- Vesicular transport through thr Golgi and presentation on the membrane
TAP transport associated with Ag processing
DRIP defective ribosomal products
Exoogenous antigen presentation process
- Pagocytosis
- Phagolysosome fusion and degradation
- Endosome contain short microbial peptides
- iMHC II is synthesized and secreted to the rER, Golgi and out on a vesicle
- Fusion of the vesicle with the endosome
- Invariant chain degradation and CLIP remains
- CLIP is removed by HLA DM and DO
- Ag is placed on to the MHC II to be presented
Lipid Ag presentation
Glycolipids and lipids are presented by MHC like molecule CD1 expressed on: thymocytes, B cells, DC, hepatocytes and epithelial cells
Glycopeptide presentation by TCR
TCR alpha/beta
only mono and di saccharides
TCR gamma/delta
only di and tri saccharides
Cross presentation
The process of presenting exogenous (viral or tumor) antigens on MHC I
in order for the activation of naive Tc cells as well and induction of cytotoxicity
Cross dressing
Occurs mainly in DC, uptake exosomes from mTEC with MHC on them and express them on the surface
Regulation on MHC I expression
IFN gamma TNF alpha and lymphotoxin
Regulation on MHC II expression
Increase exp: IFN gamma
Decrease exp: tumor cells, corticosteroids, prostaglandins
MHC is…
Polymorphic
Polygenic
Codominantly inherited
