MHC - Hudig Flashcards
What is a gene locus?
A site on a chromosome where a gene is located.
What are alleles?
Variant forms of a gene that occupy one gene locus.
What is MHC?
Major histocompatibility complex - a large multi gene complex on one chromosome. Each chromosome 6 of an individual encodes one MHC haplotype.
What is a haploype?
A haplotype is a group of genes, which is inherited together by an organism from a single parent.
How many classes of MHC (also called HLA) are there in humans?
There are three classes:
MHCI
MHCII
MHCIII
How many loci does Class I MHC have?
It has 3 loci called A, B and C. Each loci encodes an alpha chain.
How many loci does Class II MHC have?
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.
Are MHC ‘s multigenic and multallelic?
yes
Are most people heterozygous at the MHC loci?
Yes, most people express two different alleles at each of their MHC loci.
When are MHC proteins antigenic?
Only when transplanted.
Is expression of the MHC alleles co-dominant?
yes
How many different MHCI or MHCII proteins will there be on a single cell of a completely heterozygous person?
6 - There are 3 loci on each of a individual’s chromosome 6 and they are expressed co-dominately.
What is beta2 microgloobulin?
A protein that is associated with MHC but is not located in the MHC gene complex.
Describe an MHCI molecule?
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.
How are peptides held in the MHCI cleft?
By non-covalent anchoring.
What is immunodominancy?
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.
Are MHC/peptide complexes called receptors?
No, they are actually ligands for the TRC (T cell receptor).
Are MHCII proteins always present on APC’s?
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).
does MHCII protein hold large peptides?
Yes, peptides about 20-30 AA’s long.
Describe an MHCII protein?
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.
What cells lack MHCI and MHCII?
RBC’s
What cells have only MHCI?
Neutrophils, Hepatocytes, Kidney cells, cells in the brain.
What cells have MHCII? Do they also have MHCI?
T cells, B cells, Macrophages, other APC’s, Epithelial cells of the thymus. Yes.
What disease is associated with having the HLA-B27 allele?
Ankylosing spondylitis - 87 times more likely to get than someone without this allele.
What disease is associated with the HLA-DR2 allele?
Systemic Lupus Erythematosis.
What is relative risk?
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.
Name some barriers to transplantation.
- ABO blood group antigens
- MHCI and MHCII
- minor hisotcompatibility antigens
What is autograft?
Tissue grafted within one person or between genetically identical twins.
What is allograft?
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.
What is one of the major causes of graft rejection?
T cell receptors have a high frequency of recognition to foreign MHC proteins. 1/100 T cells can recognize a foreign MHC protein.
Describe MHC inheritance?
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.
What is a super- antigen?
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.
What produces super antigens?
They are made by several bacteria, including Staph.
How do superantigens bind?
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.
