Lecture 9 MHC Flashcards
MHC complexes present ____ to TCR
epitopes
TCR specifically recognize both _____ and the ____
self-MHC; antigen
MHC Class I structure
- closed
- one alpha chain (3 subunits)
- beta 2 microglobulin
- 1 transmembrane domain
How many chains make up MHC class II?
2 (one alpha, one beta)
MHC Class II sturcture
- open
- 2 chains (alpha, beta)
- 2 transmembrane domains
Side chains of peptide interact with side chains of MHC cleft via _____
noncovalent forces (electrostatic forces, hydrogen bonds, van der waals, hydrophobic)
In MHC Class ___ the peptide can hang over the cleft because it is open
II
A given MHC class I molecule will have preference for specific ___ in a particular position
amino acids
MHC class I bind peptides that are ___ aa long
8-10
MHC genes do not _____, but they are highly polymorphic/polygenic
recombine
Peptides that bind to MHC II are _____ in length
variable
The characteristic _______ of peptides in MHC are part of the interaction
overhangs
Pathogens degraded in the ______ will bind to MHC I and be presented to ___ T cells and result in _____
cytosol; CD8; cell death
What are the two types of pathogens that will bind to MHC class II?
- intravesicular pathogens
- extracellular pathogens and toxins
_______ pathogen peptides bound to MHC II will present to ___ T cells and result in activation to kill _______
intravesicular; CD4; intravesicular bacteria and peptides
_____ pathogen and _____ peptides bound to MHC II will present to ___ T cells and result in activation of B cells to secrete Ig
Extracellular; toxins; CD4
MHC I are retained in the ___ until they bind a peptide
ER
Partly folded MHC class I binds _____ until beta2 microglobulin binds
calnexin
MHC class I alpha:beta2m releases from calnexin and binds complex of _______ proteins including _____ and ______ and binds to ______ via ______
chaperone; calreticulum and ERp57; TAP via tapasin
Defective ribosomal products (DRiPs) are ______ and degraded by ______
ubiquinated; the proteasome
_____ delivers peptide fragments to the ER
TAP
MHC Class I completes its folding when ____ binds, releasing ____ and is exported to the membrane
a peptide; TAP
In MHC class II peptides come from _____
acidified endocytic vesicles
Under neutral pH, _______ are inactive, but when the endocytic vesicle fuses with the ______ and acidification occurs, they activate
endosomal proteases; lysosome
Vesicles containing ____ fuse with vesicles containing MHC II
peptides
The _______ prevents premature peptide binding to MHC class II
Invariant chain (Ii) CD74
The openness of MHC class II allows for the passage of _____ region of Ii
CLIP
The 9 chain complex includes 3 ____, 3 ____, and 3 ____
Ii chains, alpha chains, beta chains
The second function of Ii is to
target MHC class II to be trafficked to a low pH endocytic vesicle
Acid proteases initially cleave Ii to remove _____, leaving _____
trimerization domain; LIP22
Proteases further cleave LIP22 into _____
LIP10
Cleavage of LIP10 results in ____ of MHC II with ___ bound
release; CLIP
MHC II molecules bind ____ to allow for exchange of CLIP with peptides. If they do not bind peptides, the MHC molecules are _____.
HLA-DM; degraded
Structure of HLA-DM
alpha and beta chain, no groove
HLA-DM binds to the ____ of MHC II, which ______
alpha chain near the region of the floor of the peptide binding site; opens up MHC II
HLA-DM can remove ______ called peptide editing
unstably bound peptides
As they mature, dendritic cells upregulate ____ and _____
MHC Class II and LAMP-1
LAMP-1 is a ____ marker
lysosome
Class I HLAs
A, B, C
Class II HLAs
DR, DQ, DP
Polygenic
There are multiple genes that an individual possesses that makeup MHC set
Polymorphic
There are many allelic variants (for evolutionary advantage) for MHC genes
MHC class Ib present
glycolipids
What is significant about DR, DP, and DQ?
they can mix and match alpha and beta chains
variability in MHC I is found in __ chains
alpha 1 and 2
How were HLA genes discovered?
Human Leukocyte Antigens - found through antigenic differences in white blood cells between individuals
____ is monomorphic
DRalpha (Ealpha in mice)
_____ is nonvariable in the alpha chain
DR
MHC restriction is due to
- TCR and MHC interaction
- TCR and peptide interaction
____ help TCR to find MHC II
CD4
____ help TCR to find MHC I
CD8
CD1 is a gene encoded ______, is similar in structure to _____, but similar in function to _____.
outside the MHC; MHC I (presence of beta2m); MHC II
How do CD1 molecules function?
Targeted to vesicles to bind ligand
CD1 binds ____
glycolipids due to hydrophobic channel
Group 1 CD1
CD1a,b,c
Group 2 CD1
CD1d
Group 1 CD1 bind
microbial glycolipids, phospholipids, lipopeptide antigens
Group 2 CD1 bind
self lipid antigens such as sphingolipids and diacylglycerols
CD1s have ___ binding for ligands by anchoring ____ in ____
deep; alkyl chain; hydrophobic groove
CD1 bind to
T cells without CD4 or CD 8
OR CD4+ T cells
Group 2 CD1 bind to
specific TCR alpha chain (Va24-Ja18) and NK cell receptors (called invariant NKT)
Which cells have MHC II?
B cells, Macrophages, dendritic cells, epithelial cells of thymus, some T cells
____ produces greater antiviral response with overlapping B/T cell epitope
T cell
