Ch. 8 : MHC & Ag Presentation
Biology 0530 with Bungiro at Brown University
About this deck
By: Iriff Ulep
Textbook:
Kuby Immunology (Kindt, Kuby Immunology)
Created: 2010-12-10
Size: 28 flashcards
Views: 38
Textbook:
Kuby Immunology (Kindt, Kuby Immunology)Created: 2010-12-10
Size: 28 flashcards
Views: 38
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MHC Genes
humans - HLA
mice - H-2
HLA genes
Class I MHC : 3 loci
Class II MHC : 3 loci
H-2 genes
Class I MHC : 2 loci
Class II MHC : 2 loci
MHC terms (7)
Haplotype - set of MHC genes
Locus - location of 1 MHC gene
Alleles - alternative form of 1 MHC locus
Polymorphic - many alleles of gene locus in population
Syngeneic - genetically identical (same MHC haplotype)
Allogeneic - different alleles at 1+ MHC loci
Congenic - genetically identical haplotype EXCEPT at 1+ loci
MHC gene inheritance
progeny gets 1 haplotype set from each parent
MHC determines Skin Graft
Progeny can receive from either parent but cannot give back
Class I MHC structure
alpha-beta2m
"V" region : alpha 1 & 2
"C" region : Ig-like
hotdog!
anchor residues; 8-10 AA
Class II MHC structure
alpha-beta chains
"V" region : alpha 1 & beta 1
"C" region : Ig-like
Class I MHC features
all nucleated cells
beta2m & peptide dependent
8-10 AA
endogenous pathway
Class II MHC features
on specialized APCs
13-19 AA
exogenous pathway
Is there allelic exclusion?
NO
Class I MHC & NK cells
OPPOSING SIGNALS MODEL!!
Peptide binding on Class I MHC
closed binding cleft
anchor residues at end of peptide
motif on MHC
peptide can bulge out
variations in alpha 1 & 2 domains <-- peptide-binding groove
Peptide binding on Class II MHC
open binding cleft
MHC & Disease susceptibility
inbreeding = BAD
outbreeding = evolution of polymorphism = increases diversity of MHC = improves chances of resistance/survival = YAY!!!
Reduced MHC polymorphism
reduced resistance = extinction by epidemic
Genetic bottleneck
cheetahs
tasmanian devils
nonclassical CD1
presents NONPEPTIDE/glycolipid (microbacteria) to T cells
MHC Restriction
T cells MUST recognize both Ag & MHC
How do you measure T cell proliferation? (2)
3H-thymidine --> incorporation is proportional to DNA synthesized
CFSE --> decrease in fluorescence equals proliferation of T cells
Cytokine production (3)
ELISPOT
sandwich ELISA
intracellular cytokine staining
How do you measure CTL activity?
1. virus infected cells are prelabeled w/ 51Cr dye
2. once killed, 51Cr dye is released
3. amount of radioactivity is proportional to CTL activity
Self MHC restriction of CTLs - What experiment showed this?
LCM virus infected mice
Antigen Processing --> What was the experiment that showed this was necessary for Th cell activation?
no T cell activation --> fixation then adding native Ag
T cell activation --> fixation then add denatured Ag
T cell activation --> add Ab then fixate
Endogenous Pathway (Class I MHC)
1) proteins sythesized by proteasome in cytosol --> peptide transported to ER <-- TAP1/2
2) MHC produced in ER --> beta2m + alpha chain + peptide
3) Class I MHC + peptide --> golgi
Endocytic/Exogenous Pathway (Class II MHC)
1) Class II binds w/ invariant chain
2) Class II + invariant chain --> go to golgi
3) endolysosome pH drops and digests invariant chain --> CLIP left to MHC
4) exogenous peptide displaces CLIP <-- HLA-DM mediated
What happens in Golgi?
endogenous & exogenous pathways meet!!
Class I --> already loaded
Class II --> needs to be loaded
How are MHC Class I-restricted CTLs primed by viruses that don't infect DCs?
About this deck
By: Iriff Ulep
Textbook: Kuby Immunology (Kindt, Kuby Immunology)
Created: 2010-12-10
Size: 28 flashcards
Views: 38
Textbook:
Kuby Immunology (Kindt, Kuby Immunology)Created: 2010-12-10
Size: 28 flashcards
Views: 38
About StudyBlue
STUDYBLUE makes things that make you better at school.
Things like online flashcards with photos and audio.
Things like personalized quizzes and friendly reminders about when (and what) to study next.
Think of it as a digital backpack™: access to all of your study materials online and on your phone.
STUDYBLUE exists to make studying efficient and effective for every student, for free. Join us.
“I have been getting MUCH better grades on all my tests for school. Flash cards, notes, and quizzes are great on here. Thanks!”
Kathy
Kathy