Apr6 M1-HLA and Transplantation

Question 1

HLA vs MHC

Answer 1

same thing

Question 2

HLAs location in our body

Answer 2

• all nucleated cells of the body have 6 diff MHC class 1 molecules on their surface (3 types HLA A, B and C + 2 copies from each parent)
• all APCs have 6 to 8 diff MHC class 2 molecules on their surface (3 types HLA DR, DQ, DP and maybe more + 2 copies from each parent)

Question 3

how many diff MHC molecules on an APC and why

Answer 3

12-14 different

• more variety (size, shape, charge) in the peptides you can present
• can still present viral peptide even if virus mutates

Question 4

characteristics of HLA molecules (4)

Answer 4

• polymorphic (diff shapes)
• polygenic (diff genes involved in making your HLA repertoire + codominant expression)
• linkage disequilibrium
• co-dominant expression

Question 5

(EXAM) linkage disequilibrium meaning in HLA charact and significance of that

Answer 5

• many MHC subtypes genes are inherited in groups (linkage) and don’t follow Mendelian inheritance (bc are on same chromosome)
• significance = we can transplant because of that. otherwise would have too much diversity

Question 6

MHC complex location in the genome and components

Answer 6

short arm of chromosome 6

• class 1 cluster (3 genes for A, B and C HLA)
• class II cluster (many genes, including DP, DQ, DR which each have A and B genes coding them)
• class III cluster

Question 7

other genes in class II cluster and class III cluster function

Answer 7

• other impotant MHC genes

- genes important in immune system functioning

Question 8

example of function of MICE, MICC, MICB (other MHC molecules in chrom 6 short arm)

Answer 8

• involved in how NK cells recognize and kill cells

- some complement components there too

Question 9

structure of MHC class 1 molecules

Answer 9

single polypeptide chain (1 gene encoding the whole thing) (one single alpha chain)

Question 10

structure of MHC class 2 molecules

Answer 10

heterodimer or 2 chains sticking together, one A chain and one B chain (or can say alpha and beta for the protein)

Question 11

why is it that you can have up to 8 different MHC class 2 molecules on your cell surface

Answer 11

HLA DR has more than B chain molecule (2 molecules for its B chains)
so B1 from mom + B1 from dad + B2 from mom + B2 from dad that can be expressed

Question 12

cell surface molecule that MHC class 1 associates with

Answer 12

beta 2 microglobulins (same one for all MHC class 1)

Question 13

extent of the HLA polymorphism (polygenic charact of MHCs)

Answer 13

MHC class 1 A,B,C each have hundreds of alleles
MHC class 2 DQ, DP, DR a and b for each have many possibilities

Question 14

structure of the MHC class 1 part that the CD8+ sees

Answer 14

it’s a peptide binding pocket
-alpha helix around
-beta sheet in the middle peptide sits there
CD8+ T CELL SEES THE BETA SHEET

Question 15

structure of the MHC class 1 molecule

Answer 15

3 (continuous) peptides alpha 1, 2 and 3 associated non covalently to beta 2 microglobulin

Question 16

structure of the MHC class 2 part that the CD4+ sees

Answer 16

it’s a peptide binding pocket
-alpha helix around
-beta sheet in the middle peptide sits there
CD4+ T CELL SEES THE BETA SHEET

Question 17

(EXAM) maximum number of MHC molecules expressed on surface of APCs

Answer 17

• 6 class I MHC molecules

- 8 class 2 MHC molecules

Question 18

(EXAM) chance of 2 siblings matching their MHCs

Answer 18

1 in 4

Question 19

in terms of self recognition of empty MHC class 1 and 2 molecules by self NK cells and B and T lymphocytes, what is the part of the MHC molecule that is recognized

Answer 19

the alpha chain on the circumference of the peptide binding pocket (not the beta sheet)

Question 20

mixed lymphocyte reaction (also called functional typing) definition

Answer 20

mix lymphocytes of 2 people and check if they react to each other. big fight (10-20% of WBCs fighting) = chances of match are close to 0.

Question 21

tissue typing (determining someone’s MHC library for a match) old way

Answer 21

serology

• inject tissue in rabbits or mice
• categorize MHCs depending on what animals Ab recognize

Question 22

tissue typing (determining someone’s MHC library for a match) nowadays and problem

Answer 22

• genetic sequencing of the HLAs
• found specific HLA haplotypes
• we see a.a differences but we don’t know to what extent this means a mismatch, maybe it’s no visible difference

Question 23

matching goals in transplants

Answer 23

• BM transplant = 10 on 10

- immunology: want bit of mismatch bc of graft vs leukemia effect

Question 24

other genes than MHCs that may influence matching

Answer 24

minor histocompatibility antigens (or minor HLA) also called cryptic antigens (also differ from one person to another)

Question 25

matching criteria for a solid transplant

Answer 25

match class 1 A, B and C + DR (not strict for DR)

Question 26

other questions than HLA matching for a transplant (other than the 1 in 4 chances of HLA match for siblings)

Answer 26

• ABO match

- sex (male giving organ to female can be problematic because there’s an HY antigen on the Y chromosome)

Question 27

some cells in the body with no MHC class 1

Answer 27

• cornea (cells not nucleated)

- RBCs (but in blood transfusion, you match ABO which is different)

Question 28

bone marrow transplant matching criteria

Answer 28

need class 1 AND class 2 MHC matching