T cells & the Major Histocompatability Complex (MHC) Flashcards
What are B cells in their native conformation ?
B cell antigens are extracellular in their native
conformation
What are T cell antigens ?
T cell antigens are short peptide fragments of processed & presented antigen
T cells can only see antigen when it is bound to ?
T cells can only see antigen when it is bound to MHC molecules on the surfaces of antigen presenting cells
What are T cell antigens only?
T cell antigen are only protein peptides
Both extracellular & intracellular antigen is recognised ?
By T cells
Antigen processing in APCs generate ?
Pathogen protein peptides
APCs then present peptides bound ?
By Major Histocompatability
Complex (MHC) to T cells – Antigen presentation
Explain Cluster of Differentiation 4 (CD4) ?
Identifies one of the main subset of T cells that recognise peptides on MHC class II
Explain Cluster of Differentiation 8 (CD8) ?
Identifies one of the main subset of T cells that recognise peptides on MHC class I
What does CD8+ Cytotoxic T cells directly do ?
Kills infected/damaged cells (e.g. virus infection or cancer)
What does CD4+ T helper cells are ?
Master controllers that function using cytokines to control & regulate other cells
What is the subset of CD4+ T helper (Th) cell ?
5 subsets which defend against extracellular pathogens (cytokines, macrophage activation) - Th1 cells - Th2 cells - Th17 cells - Thfh cells - Treg cells
What is Human Leukocyte Antigens (HLA) ?
- Human leukocyte antigens (HLA) are genes in major histocompatibility complexes (MHC) that help code for proteins that differentiate between self and non-self
- They play a significant role in disease and immune defence
- They are beneficial to the immune system but can also have detrimental effects
What is the function of the MHC genes ?
Encode the MHC proteins on
antigen presenting cells that
present antigen
Mating with mice that had different MHC genes,
produced ?
Offspring with stronger immune systems able to combat wider variety of diseases
MHC class I & class II on antigen presenting cells present peptide antigens to?
CD4 & CD8 T cells respectively
What does MHC Class I bind to ? and found on ?
- MHC Class I Binds CD8+ T cells
- Found on all cells
What does MHC Class II bind to ? and found on ?
- MHC Class II Binds
CD4+ T cells - Found on immune APCs
Briefly explain the structure of the MHC ?
- α chain and β chain (in both MHC class II)
- Heavy chain, α chain only and β2- Microglobulin (MHC class I)
- Both consist of non-
covalent complex of two
polypeptide chains - Both have similar folding structure
Allelic MHC are inherited in linked groups called ?
Haplotypes
Who inherits haplotypes?
Each individual inherits one haplotype from each parent
How are MHC alleles expressed ?
- MHC alleles are codominantly expressed: both maternal & paternal MHC genes expressed in offspring
- This gives the best chance for an organism to have SOME capability of presenting all the possible antigen peptides it encounters
Nonmatching MHC patterns will result in ?
Rejection of transplanted tissues
MHC polymorphism tends to be clustered within groove sites of?
Peptide binding
So what do the MHC polymorphism affect ?
This affects the binding of peptide groove: This determines which antigens
can be presentation to T cells
What are the protein products of MHC genes called ?
Isotypes
Why is it that MHC class I the amino acid length is limited ?
MHC class I: Peptide ends buried within molecule limiting length to 8-10 amino acids
Is the amino acid length for MHC class II also limited?
No. The structure of MHC class II is more open so peptides extend beyond peptide binding groove - Longer & more variable length (13-25aa) than MHC class I
What is MHC Class I expressed by ?
Expressed by ALL cells (except erythrocytes & neurones)
What is MHC Class II expressed by ?
Expressed by professional antigen presenting cells (Dendritic cells, macrophages, B cells)
What specific domain of MHC class I does CD8 bind to ?
CD8 binds to α3 domain of MHC class I
What specific domain of MHC class II does CD4 bind to ?
CD4 binds the β2 domain of MHC class II
What do Cytotoxic T cells have ?
A CD8 co-receptor which cooperates with TCR to recognise peptide on MHC I
What do T helper cells have?
T helper cells have a CD4 co-receptor that cooperates with TCR to recognise peptide on MHC II
What happens when a CD8+ Cytotoxic T cell sees antigen on MHC I on potentially any nucleated cell (doesn’t have to be an immune cells) ?
TCR cell signalling & gene expression:
- Activation
- Proliferation & differentiation into Cytotoxic effector cells that can lyse infected cells
- Produce effector cytokines
What happens when a CD4+ Thelper cell sees antigen on MHC II on a professional antigen presenting cell ?
TCR cell signalling & gene expression:
- Activation
- Proliferation
- Differentiation into T helper effector cell subsets (Th1, Th2, Th17…) and ‘help’ activate other cells
- Cytokine production
