7: Ag Capture And Presentation Flashcards
Two ways innate immunity activates adaptive
- Presenting Ags to T cells
2. Co-stimulatory signals to T/B cells
Path for Ags entering periphery vs blood
Periphery -> filtered by lymph/lymphoid tissue
Blood -> filtered by spleen
Three professional APCs
DCs, macrophages, B cells
A transient professional APC
Thymic epithelial cells (also have MHC II)
Which professional APC is the only one that can activate naive T cells?
DCs
Plasmacytoid DCs function and major cytokine
Are anti-viral; produce INF type I
What three things are up regulated on DC surface when they become activated?
MHCs, CCR7, CD80 (B7)
What does HLA stand for
Human leukocyte Ag
Histocompatible tissue
Accepted by self as non-foreign
MHC genes
Tight cluster of genes that are highly polymorphic, with more than 150 known alleles
HLA gene location
Chromosome 6
How many classes of HLA genes are there?
Class I, II, and III
HLA haplotype
Total set of HLA alleles present on each chromosome
What does each allotype of the HLA gene confer?
The ability to bind different peptides for T cells to respond to
What type of expression do we have for our HLA haplotypes?
Heterozygous / co-dominant (one from mom, one from dad)
Which HLA class of genes is more diverse? Why?
Class I; they are responsible for self vs non-self recognition
Linkage disequilibrium in terms of genes
Certain alleles in a haptotype are found together significantly more frequently than expected by chance
What are class I and II HLAs important for?
Class I: intracellular pathogens + self vs non self
Class II: extracellular pathogens
Class I HLAs and NK cells
Class I HLA inhibits NK cell killing by engaging the CD94/NKG2A receptors
Class I and II genes on the HLA locus
Class I: HLA-A, HLA-B, HLA-C
Class II: HLA-DP, HLA-DQ, HLA-DR
Four proteins of class I and class II HLAs
Class I: a1, a2, a3, B2
Class II: a1, a2, B1, B2
What encodes the alpha chain and B2-microglobulin of HLA 1?
Alpha chains: HLA locus
B2 microglobulin: non-HLA genes
Which chain of class I HLA binds to the T cell? Which on the class II?
Class I: a3 binds T cell
Class II: B2 binds T cell
Which two chains form the peptide binding domain for class I and II?
Class I: a1, a2
Class II: a1, B1
Size of peptides that can bind to class I and class II HLAs
Class I: 8-10 AAs (closed ends)
Class II: 13-18 AAs (open ends)
How many alleles of a and B chains of class II HLA are expressed in a person?
6 alpha chains + 6 beta chains (3 from mom each, 3 from dad each)
On/off rates of HLA/peptide interactions
Slow on rate, even slower off rate -> peptide/HLA complex can persist long enough to contact T cells
6 Steps in Class I Ag Presentation pathway
- Proteasome degrades Ag + tags peptides with ubiquitin
- TAP and tapasin: transport peptide into ER
- A chains of HLA -> translated into ER with chaperone
- A chains and B2 globulin combine in ER
- Peptide is trimmed -> loaded into class I molecule
- Class 1 HLA - peptide complex transported to cell surface
4 Steps in Class II Ag presentation pathway
- A chains, B chains, and Ii invariant chain -> synthesized in ER -> transported through Golgi
- Lysosomal enzymes: degrades Ii to CLIP
- HLA-DM in late endosome: removes CLIP -> adds peptide
- Class II HLA - peptide complex -> transported to cell surface
Cross presentation involving DCs
DCs can display peptides on class I and II HLAs - by injesting virally-infected or transformed cells and displaying those Ags on class I HLAs
Do HLAs always carry foreign Ags?
No, without infection, they will carry self Ags that shouldn’t provoke an immune response
What two diseases/disorders are related to HLAs?
Autoimmune diseases, susceptibilities
Which HLA type I allele is present in 87% of people with Ankylosing Spondylitis?
B27
Bare lymphocyte syndrome
Deficiency in HLA class I or II expression on cells
Common defects found in neuroblastoma s
Defects of Ag-processing machinery
Common defects found in renal cell carcinomas
Class I Ag processing defects, involving TAP
