HLA

Question 1

Histocompatibility vs histoincompatibility

Answer 1

histocombatability- body recognizes transplant as SELF

HistoINcompatibility- body recognizes transplant as non self

Question 2

what do T cels recognize as antigens?

Answer 2

Portions of proteins (peptide) associated with HLA.

DOES NOT recognize antigens in free or soluble form.

Question 3

CD8+ and CD4+ binds to which class of HLA?

Answer 3

CD8+ binds class 1 (expressed on all nucleated cells)

CD4+ binds Class 2

Question 4

How do HLA genes rearrange?

Answer 4

THEY DONT REARRANGE

Question 5

HLA genes are polygenic, what are the 3 different types of class I and classII?

Answer 5

MHC class I: A, B, C
MHC class II: DR, DP, DQ

Question 6

What is a haplotype?

Answer 6

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

Question 7

What is the structure of of Class I HLA?

What makes the deep binding pocket?

Answer 7

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

Question 8

Structure of class 2 HLA?

Answer 8

Heterodimer between a1/2 and B1/2 chains. Noncovalent

Open end pocket= longer peptides (13-18 AA)

More Diverse range of peptide binding.

Question 9

Which HLA class do these types of cells show?
Erythrocytes, neutrophils, liver, macrophage

Answer 9

Erythro- none
Neutrophils- class I
Liver = Class I
Macrophage = both

Question 10

Which type of T cells will be deficient in humans with defect B 2 micro globulin?

Answer 10

Cytotoxic T cells, CD8+

B 2 microglobulin is in MHC class I. T cells need MHC in order to learn during development.

Question 11

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?

Answer 11

DR3/DR4 heterozygotes

Question 12

What will delay the progression to AIDS in people infected with HIV?

Answer 12

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.

Question 13

What types of things happen once antigen is phagocytosed by APC?

Answer 13

lose adhesive markers and up regulate CCR7

Increase expression of HLA, B7

Question 14

Which T cells are usually activated by intracellular pathogens? extracellular?

Answer 14

Intracellular: CD8+, Class I

Extracellular CD4+, Class II

Question 15

What does the TAP protein do?

Answer 15

After protein is degraded by proteasome, it is transported to the ER by the TAP protein

HLA class I

Question 16

MHC class I antigen processing steps.

What players form the peptide-loading complex?

Answer 16

1. Class I heavy a chain is stabilized by calnexin until B2-m binds.
2. Calnexin released. a and B chain form peptide loading complex with calreticulin, tapasin, TAP and ERp57
3. Peptide delivered by TAP binds to heavy chain forming the mature MHC class I molecule
4. Class I dissociates from peptide loading complex and is exported from the ER.

Question 17

Where are Class II molecules originally?

Answer 17

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.

Question 18

MHC class II antigen processing.

Answer 18

1. Invariant chain blocks binding of peptides to MHC II in ER
2. In vessicle, invariant chain is cleaved, leaving CLIP fragment in binding site
3. Vessicle merges endosomes, CLIP blocks binding of peptides
4. HLA-DM facilitates release of CLIP allowing peptides to bind.

Question 19

What is cross-presentation?

Answer 19

linking between the two pathways. Allows display of extracellular antigens on MHC class I.

Question 20

What do these cells activate when presenting antigen?

Dendritic, macrophage, B cell

Answer 20

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.