Lecture 7, MHC Flashcards
What is the physiological function of MHC?
How is this accomplished?
To present peptides to T lymphocytes
- Sampling intracellular pools of peptides and presenting them at the cell’s surface
Is MHC generally polymorphic or monomorphic?
- Polymorphic
What # c’some encodes MHC?
C’some 6
Why are MHC so polymorphic?
Because they have to present a variety of different polypeptides (which are also polymorphic)
What are the 2 broad categories of MHC loci?
What subtypes fall into each category?
- Class I MHC (1, 2, 3)
- Class II MHC (DP, DQ, DR)
*On what cells are class I MHC found?
On all nucleated cells
*On what cells are class II MHC found?
B cells, monocytes, macrophages, DCs
*What types of T cells do class I MHC-presenting cells interact w/?
CD8+ Killer T lymphocytes
*What types of T cells to class II MHC-presenting cells interact w/?
CD4+ Helper T lymphocytes
Describe the general quaternary structure of a class I MHC.
- Peptide-binding region made up of alpha-1 and alpha-2 subunits.
- Attached to cell surface via alpha-3 subunit (attached to alpha-2)
- Beneath alpha-1 is beta-2 microglobulin (not attached directly to cell surface)
Describe the peptide-binding region of class I MHC in detail (i.e. how the subunits contribute)
- Alpha-1 and alpha-2 each contribute an alpha helix
- Each also contain 4 of the 8 beta-pleated sheets each (that the Ag sits on)
Why are organ transplants always rejected if immunosuppressants are not given?
Because MHC are highly polymorphic, there are no perfect matches b/w individuals.
Describe the general quaternary structure of a class II MHC.
- Peptide-binding region made up of alpha-1 and beta-1 subunits.
- Below each, both attaching to cell surface, are alpha-2 and beta-2 subunits
Describe the peptide-binding region of class II MHC in detail (i.e. how the subunits contribute)
- Alpha-1 and beta-1 each contribute an alpha helix
- Each also contain 4 of the 8 beta-pleated sheets each (that the Ag sits on)
How long of polypeptides do class I MHC bind? Class II MHC?
- Class I: 8-10
- Class II: 13-17
What is the “anchor sequence,” w/r/t an antigen?
The conserved sequence to which the HLA actually binds the Ag (for presentation)
How many anchor sequence sites are there for peptides binding HLA class I?
2
How many anchor sequence sites are there for peptides binding HLA class II?
4
Genetically, by what pattern are HLA genes inherited? How many maternal and how many paternal loci of each HLA class are there?
Co-dominantly - 3 maternal and 3 paternal class I molecular types, as well as 3 maternal and 3 paternal class II molecular types
What is the name of a half-set of genes that are inherited from each parent (co-dominantly, in this case)?
Haplotype
Regarding organ transplantation to a boy, which of the following family members would be best to donate the organ to? Explain.
a) Mom
b) Dad
c) Brother
d) Sister
c) Brother
- Because each parent can only have up to 1/2 of the same HLA DNA as the child, they are excluded
- Sister is excluded because her X c’some differs from the male’s Y c’some
- Larger family would be ideal because there are more sibs to choose from
Explain how HLA polymorphism is important by using the e.g. of Malaria and the HLA-B53 allele.
This allele is very common in West Africa where malaria is endemic and rare where malaria is absent.
- HLA-B53, in particular, has the almost unique capacity to present particular epitope of Malaria -> survival
- Those w/o this allele have much lower survival cuz lower capacity to present peptide appropriately
(Black Death is another e.g. of this)
About how many molecular combinations are there for each class of HLA?
5,000
Cytolytic T lymphocytes (CD8+) are specific for foreign Ag plus products of class __ loci, whereas T helper (CD4+) lymphocytes are specific for foreign Ag plus products of the class __ loci.
I (all nucleated cells)
II (DCs, monocytes, macrophages, B cells)
