MHC - Hudig

Question 1

What is a gene locus?

Answer 1

A site on a chromosome where a gene is located.

Question 2

What are alleles?

Answer 2

Variant forms of a gene that occupy one gene locus.

Question 3

What is MHC?

Answer 3

Major histocompatibility complex - a large multi gene complex on one chromosome. Each chromosome 6 of an individual encodes one MHC haplotype.

Question 4

What is a haploype?

Answer 4

A haplotype is a group of genes, which is inherited together by an organism from a single parent.

Question 5

How many classes of MHC (also called HLA) are there in humans?

Answer 5

There are three classes:
MHCI
MHCII
MHCIII

Question 6

How many loci does Class I MHC have?

Answer 6

It has 3 loci called A, B and C. Each loci encodes an alpha chain.

Question 7

How many loci does Class II MHC have?

Answer 7

It has 3 loci called DP, DQ and DR. DP and DQ encode for one alpha and one beta chain. DR encodes 2 beta chains.

Question 8

Are MHC ‘s multigenic and multallelic?

Answer 8

yes

Question 9

Are most people heterozygous at the MHC loci?

Answer 9

Yes, most people express two different alleles at each of their MHC loci.

Question 10

When are MHC proteins antigenic?

Answer 10

Only when transplanted.

Question 11

Is expression of the MHC alleles co-dominant?

Answer 11

yes

Question 12

How many different MHCI or MHCII proteins will there be on a single cell of a completely heterozygous person?

Answer 12

6 - There are 3 loci on each of a individual’s chromosome 6 and they are expressed co-dominately.

Question 13

What is beta2 microgloobulin?

Answer 13

A protein that is associated with MHC but is not located in the MHC gene complex.

Question 14

Describe an MHCI molecule?

Answer 14

Each molecule has a single alpha chain associated with beta2 microglobulin. The alpha chain has 3 domains. The alpha chain domains 1 and 2 form the peptide binding cleft and holds peptides about 9-11 AA’s long. Each MHC holds different proteins and each MHC allele can bind thousands of different peptides.

Question 15

How are peptides held in the MHCI cleft?

Answer 15

By non-covalent anchoring.

Question 16

What is immunodominancy?

Answer 16

When a certain epitope within one protein is recognized by best by a person. Another person may have an MHCI that recognizes a different epitope in that same protein better.

Question 17

Are MHC/peptide complexes called receptors?

Answer 17

No, they are actually ligands for the TRC (T cell receptor).

Question 18

Are MHCII proteins always present on APC’s?

Answer 18

Yes, they are not found on all cells. They are found on APC’s and are inducible on B cells and on endothelial cells during inflammation (induced by gIFN).

Question 19

does MHCII protein hold large peptides?

Answer 19

Yes, peptides about 20-30 AA’s long.

Question 20

Describe an MHCII protein?

Answer 20

They are made up of an alpha chain and a beta chain. Both the alpha and the beta chain for the antigen binding cleft. The exception is the loci DR - it encodes an MHCII that has two beta chains.

Question 21

What cells lack MHCI and MHCII?

Answer 21

RBC’s

Question 22

What cells have only MHCI?

Answer 22

Neutrophils, Hepatocytes, Kidney cells, cells in the brain.

Question 23

What cells have MHCII? Do they also have MHCI?

Answer 23

T cells, B cells, Macrophages, other APC’s, Epithelial cells of the thymus. Yes.

Question 24

What disease is associated with having the HLA-B27 allele?

Answer 24

Ankylosing spondylitis - 87 times more likely to get than someone without this allele.

Question 25

What disease is associated with the HLA-DR2 allele?

Answer 25

Systemic Lupus Erythematosis.

Question 26

What is relative risk?

Answer 26

The incidence of a disease in individuals bearing a certain MHC locus divided by the incidence in the population of individuals lacking the allele - so even if the disease is rare, the relative risk can be high.

Question 27

Name some barriers to transplantation.

Answer 27

1. ABO blood group antigens
2. MHCI and MHCII
3. minor hisotcompatibility antigens

Question 28

What is autograft?

Answer 28

Tissue grafted within one person or between genetically identical twins.

Question 29

What is allograft?

Answer 29

Tissue grafted between allogenic or non-genetically identical individuals. Rejection usually occurs within 2 weeks without immunosuppression and grafts work better when MHC haplotype is matched.

Question 30

What is one of the major causes of graft rejection?

Answer 30

T cell receptors have a high frequency of recognition to foreign MHC proteins. 1/100 T cells can recognize a foreign MHC protein.

Question 31

Describe MHC inheritance?

Answer 31

Each person inherits an MHC haplotype from each parent. These are located on chromosome 6. There are 2 chromosomes 6’s and so 2 MHC haplotypes. The entire MHC haplotype is usually inherited as a single unit with no chromosomal crossing over.

Question 32

What is a super- antigen?

Answer 32

They are antigens that bind to a very large number of T cells non-specifically and trigger massive T cell responses. They bind to 2 sites simultaneously - regions of the MHCII chains and to a region of the T cell receptor. They bypass the normal MHCII antigen presentation.

Question 33

What produces super antigens?

Answer 33

They are made by several bacteria, including Staph.

Question 34

How do superantigens bind?

Answer 34

They bind to MHCII outside the peptide-binding groove and they bind to certain T cell receptor’s Vbeta coded by a minigene. Upon binding they trigger T cells rapidly leading to cytokine release and rapid inflammation. This can cause toxic shock syndrome and Staph food poisoning.