Hudig: MHC Flashcards
This disease is often associated with the HLA B27 locus
ankylosing spondylitis
**this is an MHC1 locus
What are the two components of an MHC Class I protein?
MHC class I alpha + beta2microglobulin
What are two components of an MHC Class II protein?
MHC class II alpha + beta protein chain
This is a large multigene complex on one chromosome
human major histocompatibility complex
MHC class I is (blank) and also (blank)
multigenic; multiallelic
How many HLA class I loci are there? What are they called?
3; HLA-A, HLA-B, HLA-C
How many different HLA-B heterozygous pairs are possible in a human?
+1,000,000
many alleles for a single locus in a population
multiallelic
many alleles frequently used in the population
polymorphic
more than one locus for the family of proteins (e.g., HLA class I A, B and C are different genes)
multigenic
The MHC I is multiallelic, multigenic, and expressed (blank).
co-dominantly
How many different MHC I proteins will there be on a single cell of a completely heterozygous person?
6
*There are 3 loci with 2 alleles at each (one from ma, one from dad) - both are expressed on the cell surface due to co-dominance
Where in the body would you find a cell with MHC I molecules?
In all cells except RBCs
Describe the structure of the MHC I proteins
1 alpha chain (comprised of three parts) attached to 1 Beta2-microglobulin
Which portion of the MHC I protein forms a peptide-binding cleft?
the alpha chain
**this cleft can hold peptides of 9-11AA
What is unique about each MHC allelic protein?
each MHC allelic protein will hold slightly different peptides
**furthermore, each MHC allele can bind thousands of different peptides
Why is MHC I allelic variation important?
It maximizes the ability of MHC molecules to present a DIVERSE array of antigenic peptides
**side note: most people inherit MHC I alleles that are able to bind some influenza peptides; if not… SOL
What is meant by MHC antigen restriction?
A memory CTL must match both the antigen (peptide) and the MHC I protein in order to kill.
**this makes it challenging to test CTL anti-viral vaccines, because you can only use them with target cells that have the same MHC I as the immune donor of the CTLs
MHC Class II proteins are always present on (blank) and are inducible in (blank) during inflammation
APCs (macrophages, dendritic cells); endothelial cells
Describe the structure of the MHC II protein.
1 beta chain, 1 alpha chain; open-ended so it can hold large peptides of 20-30AA
MHC Class II is also (blank) and (blank), much like MHC Class I
multigenic; multiallelic
How many HLA class II loci are there? What are they called?
3; DP, DQ, DR
What cells lack both MHC I and II?
RBCs
What cells have only MHC I?
neutrophils
hepatocytes
kidney cells
brain cells
(cells that are not antigen presenting cells)
What kind of cells have MHCII?
cells in lymphoid tissues T cells B cells macrophages APCs
Do cells with MHC II also have MHC I?
Yes
**all cells have MHC1 except RBCs
List some diseases associated with certain HLA alleles
ankylosing spondylitis
Type I diabetes
systemic Lupus Eryhtematosis
Why are MHC I and II barriers to organ transplantation?
T cells have a high frequency of recognition of foreign MHC molecules!!
Tissue grafted within one person
or between genetically identical mice or twins
Usu 100% successful
autograft
tissue grafted between HLA (& other loci) allogeneic individuals
Usu rejected within 2 weeks if no immunosuppression
allograft
When do you have the best chance of survival after an allograft?
when MHC haplotypes are matched
T/F: Even when you have complete HLA matching, there are other genetic differences that may cause graft rejection.
True
T/F: There is an MHC Class III that we are not too concerned with, because these genes are mostly nonallelic.
True
Linked sets of genes usually inherited as one unit, one is inherited from each parent
haplotypes
How many MHC haplotypes does each person have?
2
*one from ma, one from dad
How is the MHC haplotype usually inherited?
as one single unit, as if it were only one gene
What are superantigens?
they are antigens made by several bacteria, including Staph, that bind to a very large number of T cells and trigger MASSIVE T cell responses
**they sort of bypass normal MHC-peptide presentation and activate T cells instantly
Superantigens bind to 2 sites simultaneously. What are they?
- regions of MHC II chains
2. T cell receptor V betas
Superantigens bypass normal (blank) and often cause disease
MHC II antigen presentation
*no need to process the peptide and present it as a foreign body
Bypass normal antigen-presentation and trigger T cells rapidly, including cytokine release. Cytokine release causes diseases like toxic shock syndrome and staph. food poisoning
superantigens
What are two conditions that can be caused by superantigens?
rapid food poisoning by staphylococci enterotoxin
toxic shock syndrome
Which subclass of TCRs can superantigens bind t?
Vbetas (minigenes) contained on T cell receptors
