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Origin and Maturation: how T cells become Helpers or Killers

T cells go through a complicated maturation process that allows them to distinguish cells that belong to the body and are healthy from those that aren't healthy or don't belong to the body at all! The maturation process also determines whether they become Helper or Killer T cells.


T cells come from stem cells in the bone morrow and are sent to the thymus to mature.  The “T” in T cells is named after the thymus. The thymus is an organ behind your breastplate which helps the naïve T cells learn to develop into a specific T cell. The most important lesson the T cell learns is how to distinguish between healthy self and nonself. Basically they learn to only attack intruder organisms, infected cells, and not healthy cells! Only T cells that mature into specific cells are allowed to leave the thymus. This is one of the main reasons why our very potent immune system doesn’t attack our own bodies. 

What makes a T cell?

T cells identify cells by the proteins that the cells produce and have on their membranes - the antigen (read about antigens and identifying cells). Healthy body cells produce self antigens, and unhealthy body cells or germs produce nonself antigens. Most body cells have a special group of proteins - the Major Histocompatability Complex whose job is to display these proteins. The MHC is a common group of proteins the T cells can grab onto to observe the antigen.

So, our T cells need to:

  1. 1- T cells need to bind strongly to the MHC complex of the cells to have time to identify the antigen presented.
  2. 2- T cells must bind strongly with a nonself antigen to start an immune reaction
  3. Or, T cells must not bind strongly to a self antigen, so the T cell will moves on.

So T cells must be able to bind strongly to the MHC complex and strongly to an unknown nonself antigen.

The T cell receptor site (TCR) actually contains two sites: one that binds with the MHC complex (to bind cells ), and a second receptor site that binds with the antigen displayed (to recognize antigens ). Each T cell has many TCR binding sites.

The maturation of the T cells assures that these abilities are developed before releasing them to the body.

Positive selection - Learning Tolerance
When T cells arrive in the thymus they have two kinds of MHC-receptors, CD4 and CD8. In the thymus they are exposed to a wide variety of peptides (MHC I and II among others) that are like what they will find in the fluids of the body or part of cells. The T cells must be able to bind one kind of protein available to be able to recognize cells that belongs to the body. If a T cell's CD4 receptors binds a protein, its CD8 receptors degenerate and the T cell goes on to be a Helper T cell. If its CD8 receptor binds a protein, then the T cell stops making CD4 receptors and the T cell goes on to be a cytotoxic T cell.

If the immature T cell doesn’t bind to any protein then it means that it cannot recognize self proteins, and is triggered to die. Only T cells that bind strongly to any kind of MHC receptor site receive the survival signal (ones that don’t undergo apoptosis).

It is said then the immune cells become tolerant of self proteins.

Negative Selection - Blocking Self-Antigen Recognition
In the thymus, the T cells are also exposed to many different types of self antigen peptides - examples of the different healthy proteins they will find in the body. If the T cells bind too strongly to self proteins they must also be destroyed immediately. Their extra-strong affinity can mean that they are more likely to mount an attack against the cells that belong to the body (autoimmunity).

So, T cells are matured to bind either MHC I (becoming Killer T cells) or MHC II (becoming Cytotoxic T cells) and to not bind self antigens presented in these MHCs.

The antigen-binding site of each T cell is specific. It will only bind one kind of nonself antigen. This means the body produces millions of varieties of T cell antigen-binding sites, to create antigen-binding sites that will match and bind strongly whatever nonself antigen we may encounter!


Our immune cells learn to be tolerant to what belongs to the body. When this mechanism goes wrong, and the immune system starts an attack on itself, it is called an auto-immune disease. Our bodies can also acquire tolerance, when the body learns to tolerate external substances or cells, like in the case of a pregnant mother whose immune system must tolerate her growing baby.

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