TCR and MHC molecules Flashcards
What are the two major T-cell sub population?
CD4+ T-cells:
- Helper T-cells, TH-cells
CD8+ T-cells:
- Cytotoxic T-lymphocytes, (CTL)
What do T-cells express on their surface apart from TCR and what is it responsible for? (2)
CD3
Responsible for signalling
What are the principles of antigen recognition by T-cells? (4)
Antigen is recognised by the T-cell receptor (TCR)
Antigen is presented to T-cell by second cell - this cell functions as an antigen presenting cell (APC)
Antigen is presented by MHC molecules on the APC cell surface
Antigen is not native but is instead processed: proteins are processed by proteases into peptide fragments
What is the difference between the role of MHC class I and class II molecules? (2)
MHC class II molecules present antigens to CD4+ T-cells
MHC class I molecules present antigens to CD8+ T-cells
Describe the structure of a T cell receptor (4)
Integral membrane protein that is anchored to the surface of a T cell
Two chains held together by disulphide bond
Each chain has a variable and constant domain
The two variable domains combine to form the antigen recognition site
What is CD3? (3)
Component of TCR complex
Transduce a signal when TCR interacts with antigen causing T cell to become activated
What are T-cell epitopes? (4)
T cells recognise short contiguous peptides, typically 8 to 12 amino acids in length
Not possible to co-crystallise TCR and epitope as with antibodies and their antigens
Studies of the crystal structure of MHC molecules, short amino acid peptide co-crystallised in a “cleft”
Functional assays of T-cells, revealed that they only respond to short contiguous peptides
What can be the possible structure of antigen? (2)
Can be from anywhere in the folded structure of a protein, ie can be either surface exposed or buried within the folded structure of the protein
How to identify a T cell epitope in an antigen? (5)
Antigen, APC incubated with T cell clone
This produces a response
Synthesise overlapping
peptides representative
of complete sequence
Test each epitope
individually for
T-cell response
Epitope
identified
What is MHC class I antigen presentation important for? (1)
Important in immune response to viruses and cancer
Where are MHC class I molecules expressed? (1)
MHC class I molecules are expressed on the cell surface by all nucleated cells
Function of MHC class I molecules (2)
Present intracellular (endogenous) antigens from within the antigen presenting cell eg viral proteins and tumour antigens
Describe the MHC class I antigen presentation pathway (3)
Virus synthesise their own proteins
Viral proteins chopped up by proteasome to produce peptides
These are translocated in lumen of endoplasmic reticulum and loaded onto MHC class I molecules which present the antigen
Where are MHC class II molecules expressed? (2)
Expressed on the cell surface of ‘professional’ antigen presenting cells: B-cells, dendritic cells and macrophages
Function of MHC class II molecules (2)
Present extracellular (exogenous antigens) that are taken up by endocytosis from outside of the cell
Describe the MHC class II antigen presentation pathway (5)
Antigen taken up by endocytosis and delivered into endosomes where it is chopped up into peptide fragments by proteases
MHC molecule associated with invariant chain
This traffics newly synthesised MHC molecules to endosomes
It is then chopped up itself and therefore, opens up peptide binding site for antigenic peptide to bind
MHC molecules loaded with peptides derived from antigen
Displayed on cell surface
Compare MHC class I and II presentation (5)
Check one note:
MHC and TCR lecture
Describe structure of MHC class I molecules (3)
Expressed on the plasma membrane
MHC molecules have 4 extracellular domains, 2 of which form the peptide binding site
MHC class I molecules comprise the heavy chain and beta-microglobulin
Describe structure of MHC class II molecules (3)
Expressed on the plasma membrane
MHC molecules have 4 extracellular domains, 2 of which form the peptide binding site
MHC class II molecules comprise the alpha and beta chains
What are MHC molecules in terms of genes? (1)
Polygenic: there is more than one gene for the MHC class I and MHC class II molecules
Alleles expressed Co dominantly expressed
What is the major histocompatibility Complex (MHC) (4)
Complex of genes encoding for proteins involved in immunity
Class I region codes for MHC class I heavy chains HLA-A, -B, & -C (HLA: human leukocyte associated)
Class II region codes for MHC class II molecules HLA-DR, -DP & -DQ
Class III codes for some complement proteins and some cytokines
Why are MHC molecules polygenic and polymorphic? (3)
Each MHC molecule can bind and present a distinct repertoire of antigenic peptides to T-cells
By expressing up to 6 MHC class I and 6 MHC class II molecules we increase the number of different peptides we can present to T-cells
There are millions of different combinations of MHC alleles: makes it difficult for pathogens to evolve their protein sequences to prevent the presentation of their antigens
How and why can MHC molecules cause problems in transplation? (4)
Mismatched MHC molecules make tissues and
organs histoincompatible
The successful transplantation of organs or bone marrow is more likely when MHC molecules are
closely matched between donor and recipient
Mismatched MHC transplants are more likely to be
rejected
Ideal donors for transplants are identical twins
(100% matched MHC)
