6 - T lymphocytes and antigen recognition Flashcards
What do T lymphocytes do?
T lymphocytes destroy intracellular pathogens
How do T lymphocytes recognise infected cells?
They recognise infected cells using a specific receptor on their cell surface, the T cell receptor (TCR).
What is the structure of the TCR?
The TCR resembles a membrane-bound form of an antibody Fab fragment in structure.
It consists of two polypeptide chains each containing a variable domain and a constant domain.
Why is there a diverse T cell repertoire?
There is a very large number of different TCR’s present in each individual
What happens to the antigens that T cells recognise?
- They are processed; that is they are small peptide fragments derived from larger proteins (some specialised T cells are able to recognise non-peptide antigens).
- Processed antigen is presented to T cells on cell surfaces by specialised molecules called MHC molecules.
What are the 2 types of T cell?
- Use CD4 co-receptor, see peptide antigen presented by MHC class II (“class II restricted”)
- Use CD8 co-receptor, see peptide antigen presented by MHC class I (“class I restricted”)
What do Co-receptor molecules do?
They bind to an invariant (non-polymorphic) part of the appropriate type of MHC molecule, increase the avidity of T cell-target cell interaction, and are important in signaling.
What are CD8+ T cells involved with?
What are they called?
Also known as cytotoxic T lymphocytes, CTL or Tc
- They are cytotoxic and kill target cells; they also secrete cytokines e.g. interferon-γ.
What are CD4+ T cells involved with?
What are they called?
Also known as T helper cells or Th
- They secrete cytokines which may recruit cells of innate immunity, help activate macrophages, and amplify and help CTL and B cell responses.
CD4+ T cells may be subdivided into the Th1 type or Th2 type, depending on the cytokines they produce.
What happens during T lymphocyte development?
T lymphocytes develop in the thymus from bone marrow-derived precursors.
1. They do not express a TCR or CD4 or CD8 (double negative stage).
2. As they develop they move from the thymus outer cortex towards the inner medulla.
3. The formation of a TCR, using gene segment recombination similar in principle to antibody gene rearrangement (although different gene segments are used).
4. Cells which express a TCR express both CD4 and CD8 (double positive stage).
5. Cells then undergo selection for those which express a useful TCR: positive selection allows the survival of cells whose TCR recognises self MHC, negative selection removes cells whose TCR recognises self MHC very strongly (to avoid dangerous reaction to self and autoimmunity).
Only about 5% of developing T lymphocytes (thymocytes) survive these selection processes and move into the circulation as mature single positive either CD4+ or CD8+ cells.
What is MHC?
Major Histocompatibility Complex.
A group of tightly linked genes important in adaptive immune response.
They are a marker of ‘self’.
What are the 2 classes of MHC molecules?
Class I - classical transplantation antigens
Class II - regulatory, controlling the ability to mount immune responses
What MHC do cell express?
Nearly all cells express MHC class I (at various levels)
MHC class II is only normally expressed on “professional” antigen presenting cells (APC), i.e. dendritic cells, macrophages and B lymphocytes.
What do MHC display?
A processed sample of the internal contents of a cell at the cell surface…
- Indicated the health of the cell
- For possible recognition by the immune system (T cells)
The human MHC is also known as what?
HLA - human leukocyte antigen.
Human MHC genes are highly polymorphic.
What does polymorphic mean?
Variable within the population.
What is an MHC haplotype?
A group of MHC genes linked together on one chromosome.
Humans are diploid so we have 2 MHC haplotypes.
Where does diversity exist in MHC molecules?
Diversity is in the population, NOT within an individual.
MHC class I structure?
1 transmembrane region
1 beta chain(left) and 1 alpha chain(right) at the bottom
2 alpha chains on top
Peptide binding cleft at the top
MHC class II structure?
2 transmembrane regions
1 alpha chain(left) and 1 beta chain on the bottom
1 alpha chain(left) and 1 beta chain on the top
Peptide binding cleft at the top.
What are the 2 main pathways of antigen presentation?
Antigens in different locations require different responses.
ENDOGENIOUS antigens - cytoplasm Presented by MHC class I to CD8 T cells
EXOGENIOUS antigens - external to the cell Presented by MHC class II to CD4 T cells
What does TAP stand for?
Transporter for antigen processing
What does CLIP stand for?
Class II associated invariant chain peptide
Brief summary - antigen recognition by T and B cells?
B cells - Surface antibody receptor, intact extracellular antigen.
T cells - Surface T cell receptor, processed antigen by MHC molecules.
