Lecture notes
Antigen recognition by T cells
- Module
- Mechanisms of pathology
- Institution
- Aston University, Birmingham (Aston)
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Antigen recognition by T cells.T cells are like B cells because:
• Both T and B cells are classed as lymphocytes.
• They originate from the same lymphocyte progenitor in the bone marrow during the
process of hematopoiesis.
• They both have immunoglobulin antigens on their surface.
• Both B cell and T cell receptors are formed using gene rearrangement strategies
during development and maturation of those naïve T and B cells and that results in
those cells having one specific antigen binding receptor on their cell surface.
• Both T and B cells have a clonality to them. You have a diverse population of
different T and B cells all of which have one T or B cell specific to them on their cell
surface. So you have a population of T and B cells which are individual clones.
• Only a single species of receptor exists on any one cell.
T cells are unlike B cells because:
• T cells develop within the thymus, this is a specialized structure in the body which is
a T cell school.
• The very naïve progenitors leave the bone marrow, clone to the thymus where they
go through rounds of maturation and expansion and gene rearrangements that they
require in order to generate those T cell receptors on the cell surface.
• T cells also recognize different antigens to B cells.
• The B cell receptor can bind native antigens whereas the T cells require those
antigens to be processed and broken down to smaller chunks.
• T cell receptor only recognizes small peptides so therefore only binds to key epitopes
within those peptides that have been presented to them.
• Peptides have to be presented in terms of being bound to the MHC molecules on the
cell surface of the antigen presenting cell.
• And this requires a good interaction between our T cell and the antigen presenting
cell in order for that T cell receptor to get the right set of signals.
• And therefore, instruct the T cell to modulate the antigen presenting cell.
• The T cell receptors are always membrane bound. They are never present solubley
that only happens in a B cell receptor.
• when the B cell receptor mature in the plasma cells and release the B cell receptors
antibodies.
• B cell receptor can go through rounds of mutation/class switching to make it become
a higher affinity antibody.
• Therefore, it is able to bind to an antigen more tightly.
• Whereas a T cell receptor once it has been made and it is expressed on a clonal T
cell, it is always fixed at that point.
• You can never remutate you're T cell receptor.
• So, once it is made that structure is maintained throughout that clones life.
Fixed TCR are a problem as we age.
• Fixed T cell receptor epitope binding can be a problem as we age.
• T cell repertoire- clones of T cells that you contain within your body are usually in
place by the time you hit puberty.
, • This is because after puberty (after the age of 20/21), you’re thymus starts to shrink
and this seems to be a natural physiological phenomenon but it also means your
ability to make new naïve T cells as you get older decreases.
• So we see changes in T cell compartment based on the inability to make as many
new naïve T cells because of thymic evolution.
• As we age, we are constantly being exposed to different pathogens, throughout our
lives.
• And therefore drive innate and adaptive immune responses.
• And those adaptive immune responses ultimately lead to the generation of memory
T and B cells.
• In the T cell pool there is a limited space of the number of T cell clones that the
body can contain.
• We only have a finite amount of space in our lymph nodes and other secondary
tissues to hold those naïve T cells.
• As we generate those adaptive immune responses we will expand our T cell pool to
contain memory T cells once the adaptive immune response is finished.
• We want to keep the memory T cells because these are the ones that will react much
quicker when the encounter the pathogen for the second time.
• By expanding those memory B cells upon recounter with the antigen, the memory B
cells take up more space and this means there is less space for naïve T cells.
• When we are born, because we have not seen that many antigens at that present
time and environmental pathogens our T cell repertoire is full of naïve T cells, all of
which are these clonal cells which express one particular T cell receptor.
• As we age, and go through cycles of encountering pathogens, gradually we start
keeping the memory cells and our population dynamics changes.
• We go from a population of naïve T cells from when we are born.
• As we age these naïve T cells are replaced by memory T cells, that we keep so that
we can react to the pathogens quicker.
• This means that naïve T cells which have not been activated yet are deleted to make
space for the new memory T cells therefore maintaining our lifelong protection.
• In elderly their T cell compartments are full of memory cells, there is often not a lot
of naïve T cells left.
• This is one reason why the elderly are more susceptible to infections because there
populations of naïve T cells are greatly reduced and they do not have the ability to
generate lots of new naïve T cells because there thymus has become much smaller
and therefore the thymic output is greatly reduced.
• This is a rate limiting step of the adaptive immune response because it is great when
you are young and healthy and as you age the immune response slowly decreases.
• This is particularly important in vaccination for the elderly, as this leaves the elderly
population vulnerable to pathogens if we cannot drive a good immune response
from them
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