L5 MHC structure and function + peptide binding

Question 1

what are the functions of MHCs?

Answer 1

MHCs activate T cells by presenting peptide fragments derived from pathogens on their cell surface, to TCRs. Act as ligands. Infections keep MHCs upregulated.

Question 2

what are mhc class 1s recognised by, where are they expressed and what is their source of peptide?

Answer 2

mhc class 1s are recognised by cd8+ (tc) T cells, expressed on all nucleated cells and their source of peptides is from proteins synthesised within the cell (endogenous). if there is an infection their peptides are from viruses that replicate within the cell.

Question 3

what are mhc class 2s recognised by, where are they expressed and what is their source of peptide?

Answer 3

mhc class 2s are recognised by cd4+ (th) cells, expressed on antigen presenting cells, b cells, macrophages and dendritic cells. source of peptides is from proteins taken up by the cell (exogenous). if infection, from extracellular bacteria.

Question 4

what happens if an mhc is not bound to a peptide?

Answer 4

mhcs are unstable if no peptide is bound so will fall apart. all mhcs on the cell surface contain peptides. in the absence of pathogens all peptides are derived from self proteins.

Question 5

steps of mhc function?

Answer 5

antigen processing turns antigens into smaller fragments.

no infection= mhc class1 present peptides from self proteins
viruses= some mhc class 1 will present peptides from viral proteins which is recognised by cd8+ and infected cell is then killed.
mhc class 2: phagocytosis of bacteria- antigens are loaded onto mhc cells and transported to macrophage surface. some mhc class 2 will present peptides from bacterial proteins. recognised by cd4+ which releases cytokines and aids in destruction by further activating macrophages and other immune cells.

Question 6

antigen presenting by mhc class 2 on b cells?

Answer 6

antigens bind to b cell receptors. b cells internalise antigens then antigen processing occurs. antigens are loaded onto mhc class 2. some mhc class 2s will present the peptides from bacterial proteins. recognised by cd4+ which secretes cytokines and so aids in antibody production.
along with mhcs, costimulatory signals are needed to activate t cells.

Question 7

antigen presenting by dendritic cells?

Answer 7

Dendritic cells are proffessional antigen presenting cells. dendritic cells in the periphery needed for recognition and ingestion of pathogens. in secondary lymphoid organs they extend long processes known as dendrites. (enhances interactions with t cells) there is antigen presentation to both cd4 and cd8 t cells.

Question 8

mhc gene regions?

Answer 8

mhc genes are on chromosome 6. ver long: 3.6x10^6 base pairs long. 224 gene loci-128 expressed and 51 in the immune system.
polygeny- multiple genes for mhc class1 and class 2. called HLA (human leukocyte antigen genes.

Question 9

mhc class 2 hla?

Answer 9

HLA- DR,DP+DQ
alpha and beta chains are encoded in mhc region.

Question 10

mhc class 1 hla?

Answer 10

HLA- A,B,C
alpha/heavy chain is encoded in mhc region.

Question 11

polymorphic?

Answer 11

highly polymorphic- high variation in specific allele of hla. mhc protein variants are present in the population. these proteins have the same structure but differ in 1-20 aa. most variation is in peptide binding domain. o can bind to lots of peptides and present different antigens so enhances immune system ability to recognise and respond to different pathogens.
each person has 6x mhc class 1 and 6x mhc class 2 or more. 3x on one chromosome and 3x on another.

Question 12

co-dominance?

Answer 12

mhc are co dominantly expressed from bith chromosomes so individuals can express up to 6 mhc class 1 molecules.

Question 13

haplotype?

Answer 13

each persons mhc= haplotype- the combination of mhc alleles inherited from parents. each person has 2 haplotypes, 1 on each chromosome. s

Question 14

structure of mhc class 1?

Answer 14

has 2 subunits: transmembrane protein: alpha/heavy chain linked to a soluble beta-2-microglobulin protein which keeps the mhc stable until a peptide binds to it. made of 1 alpha chain folded into 3 domains. alpja1 and alpha2= peptide binding group. alpha 3= transmembrane domain-anchors mhc into cell membrane.

Question 15

structure of mhc class 2?

Answer 15

2 subunits: transmembrane protein alpha chain and tm protein beta chain. a1= peptide binding domain. b2= immunoglobulin like domains. the position between alpha 1 and beta 1 us the peptide binding group.

Question 16

structual difference between them?

Answer 16

mhc class 2 peptide binding group is closed at both ends. class 2 is open at ends. structure of this determines how big a peptide is. for an mhc class 1: peptide binding groove is 8-10 aa long. mhc class 2: 13-24 aa long. peptides can stick out.

Question 17

what happens to mhcs on the cell surface during an infectious + how do t cells recognise them?

Answer 17

once a peptide is loaded no swapping once mhc is on the cell surface, mhcs have a certain half life so in infection they are replaced at the surface with a mhc with a pathogen derived peptide. t cell recognition of peptides is mhc + peptide restricted. so t cell contacts both mc and peptide therefore the peptide is an essential subunit of mhc.

Question 18

characteristics/ motifs of peptides binding to mhc class 1?

Answer 18

• 8-10 aa long
• hydrophobic or basic residues at c terminus
• every mhc class 1 allele has its own peptide binding motif with specific anchor residues that interact with polymorphic mhc residues
• interaction with mhc is stabilised by: nh+ and cooh- terminus

Question 19

what are anchor residues?

Answer 19

anchor residues are specific amino acids within the peptide that fit into corresponding pockets within the peptide binding groove, allowing a peptide to bind. they are similar for peptides that bind to the same mhc molecule. ?

larger amino acids can cause the peptide to bulge- check if for mhc class 1

Question 20

mhc class 2 peptide binding motifs?

Answer 20

• 13-24 aa
• protrude from the groove.
• NH+ COO- do not contribute
• interaction with mhc is stabilised by: peptide backbone with conversved mhc residues, anchor residues with polymorphic mhc residues.
• mhc binds to 10^5-10^6 different peptides. mhc polymorphism localised to peptide binding cleft. s unique pattern of pockets in pbc + peptides presented by each allele are different. so particular combination of mhc alleles inherited determines peptides displayed to t cells (responsiveness)