HLA Flashcards
Histocompatibility vs histoincompatibility
histocombatability- body recognizes transplant as SELF
HistoINcompatibility- body recognizes transplant as non self
what do T cels recognize as antigens?
Portions of proteins (peptide) associated with HLA.
DOES NOT recognize antigens in free or soluble form.
CD8+ and CD4+ binds to which class of HLA?
CD8+ binds class 1 (expressed on all nucleated cells)
CD4+ binds Class 2
How do HLA genes rearrange?
THEY DONT REARRANGE
HLA genes are polygenic, what are the 3 different types of class I and classII?
MHC class I: A, B, C MHC class II: DR, DP, DQ
What is a haplotype?
set of genes on one chromosome. The specific A, B, C, DR, DP, and DQ received from one parent
All will be expressed. Co dominant
What is the structure of of Class I HLA?
What makes the deep binding pocket?
Hetero dimer between a1, a2, a3 and B micro globulin
a1 and a2 make binding site. Dictated by conformation. and depends on AA orientation in pocket
Structure of class 2 HLA?
Heterodimer between a1/2 and B1/2 chains. Noncovalent
Open end pocket= longer peptides (13-18 AA)
More Diverse range of peptide binding.
Which HLA class do these types of cells show? Erythrocytes, neutrophils, liver, macrophage
Erythro- none Neutrophils- class I Liver = Class I Macrophage = both
Which type of T cells will be deficient in humans with defect B 2 micro globulin?
Cytotoxic T cells, CD8+
B 2 microglobulin is in MHC class I. T cells need MHC in order to learn during development.
Depending on the type of HLA you have, your risk for autoimmunity can go up or down.
Which HLA alleles are more at risk for type I diabetes?
DR3/DR4 heterozygotes
What will delay the progression to AIDS in people infected with HIV?
Heterozygosity of HLA class I. Cuz CD8+ binds viral peptide.
homozygous for one (ex. HLA A same from mom/dad) = increased rate
homozygous for 2 or 3 = even faster rate of progression.
What types of things happen once antigen is phagocytosed by APC?
lose adhesive markers and up regulate CCR7
Increase expression of HLA, B7
Which T cells are usually activated by intracellular pathogens? extracellular?
Intracellular: CD8+, Class I
Extracellular CD4+, Class II
What does the TAP protein do?
After protein is degraded by proteasome, it is transported to the ER by the TAP protein
HLA class I
MHC class I antigen processing steps.
What players form the peptide-loading complex?
- Class I heavy a chain is stabilized by calnexin until B2-m binds.
- Calnexin released. a and B chain form peptide loading complex with calreticulin, tapasin, TAP and ERp57
- Peptide delivered by TAP binds to heavy chain forming the mature MHC class I molecule
- Class I dissociates from peptide loading complex and is exported from the ER.
Where are Class II molecules originally?
In the ER but cannot bind peptide because of the invariant chain and CLIP fragment block the binding site.
Meets peptides in vesicles because they were phagocytosed.
MHC class II antigen processing.
- Invariant chain blocks binding of peptides to MHC II in ER
- In vessicle, invariant chain is cleaved, leaving CLIP fragment in binding site
- Vessicle merges endosomes, CLIP blocks binding of peptides
- HLA-DM facilitates release of CLIP allowing peptides to bind.
What is cross-presentation?
linking between the two pathways. Allows display of extracellular antigens on MHC class I.
What do these cells activate when presenting antigen?
Dendritic, macrophage, B cell
Dendritic- activate Naive T cell> clonal expansion and differentiate to effector T cell
Macrophage: actiavte Effector T cell > activates macrophage killing
B cell: activates Effector T cell > B cell activation and antibody production.
