Apr6 M1-HLA and Transplantation Flashcards
HLA vs MHC
same thing
HLAs location in our body
- 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)
how many diff MHC molecules on an APC and why
12-14 different
- more variety (size, shape, charge) in the peptides you can present
- can still present viral peptide even if virus mutates
characteristics of HLA molecules (4)
- polymorphic (diff shapes)
- polygenic (diff genes involved in making your HLA repertoire + codominant expression)
- linkage disequilibrium
- co-dominant expression
(EXAM) linkage disequilibrium meaning in HLA charact and significance of that
- 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
MHC complex location in the genome and components
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
other genes in class II cluster and class III cluster function
- other impotant MHC genes
- genes important in immune system functioning
example of function of MICE, MICC, MICB (other MHC molecules in chrom 6 short arm)
- involved in how NK cells recognize and kill cells
- some complement components there too
structure of MHC class 1 molecules
single polypeptide chain (1 gene encoding the whole thing) (one single alpha chain)
structure of MHC class 2 molecules
heterodimer or 2 chains sticking together, one A chain and one B chain (or can say alpha and beta for the protein)
why is it that you can have up to 8 different MHC class 2 molecules on your cell surface
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
cell surface molecule that MHC class 1 associates with
beta 2 microglobulins (same one for all MHC class 1)
extent of the HLA polymorphism (polygenic charact of MHCs)
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
structure of the MHC class 1 part that the CD8+ sees
it’s a peptide binding pocket
-alpha helix around
-beta sheet in the middle peptide sits there
CD8+ T CELL SEES THE BETA SHEET
structure of the MHC class 1 molecule
3 (continuous) peptides alpha 1, 2 and 3 associated non covalently to beta 2 microglobulin
structure of the MHC class 2 part that the CD4+ sees
it’s a peptide binding pocket
-alpha helix around
-beta sheet in the middle peptide sits there
CD4+ T CELL SEES THE BETA SHEET
(EXAM) maximum number of MHC molecules expressed on surface of APCs
- 6 class I MHC molecules
- 8 class 2 MHC molecules
(EXAM) chance of 2 siblings matching their MHCs
1 in 4
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
the alpha chain on the circumference of the peptide binding pocket (not the beta sheet)
mixed lymphocyte reaction (also called functional typing) definition
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.
tissue typing (determining someone’s MHC library for a match) old way
serology
- inject tissue in rabbits or mice
- categorize MHCs depending on what animals Ab recognize
tissue typing (determining someone’s MHC library for a match) nowadays and problem
- 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
matching goals in transplants
- BM transplant = 10 on 10
- immunology: want bit of mismatch bc of graft vs leukemia effect
other genes than MHCs that may influence matching
minor histocompatibility antigens (or minor HLA) also called cryptic antigens (also differ from one person to another)
