Although it may seem obvious, identifying cancer and pathogen-specific epitopes, or TCRs is a fruitless endeavor. The adaptive immune system will always have the necessary clones to identify cancer or pathogen due to the diversity of T cell or B cell types. In addition, & nbsp,
With one exception, epitopes have no meaning associated with them. Andnbsp, when the aforementioned epitope is the self. There will be various sets of self-epitopses in each body. Thymic Tregs are trained to stop any T cell activity against those epitopes in the periphery because the thymus encodes every self-episode necessary for the host’s survival. This is known as tolerance, and it is specific to the antigen [ epitope ]. & nbsp,
What then prevents people from reacting effectively to pathogens or cancers? Tregs are frequently, but incorrectly, thought to prevent T or B cells from effectively responding to pathogens or cancers. However, tregs only stop the anti-self response, which is an epitope-specific action. & nbsp, Therefore, by definition, we cannot hold Tregs accountable if they perform their duties as required. However, it is unrelated to cancer or pathogens, which undoubtedly have other epitopes besides the self that we refer to as nonself. Why then can’t everyone effectively fight off cancer cells or pathogens if they express non-self epitopes that are always picked up by the adaptive immune system?
This is due to the fact that T cells themselves stop it. Yes, in some circumstances, T cells— not Tregs — prevent an effective response to cancers or pathogens. What exactly are those circumstances? When polarized T helper cells interfere with other T cells’ ability to function, these conditions occur. A pathological state is polarization. A polarized T cell’s effect on other T cells is epitope non-specific, which means that a cancer – or pathogen-unspecific T helper cell won’t be able to properly function if it has epitopices B, C, D, E, F, etc. Treg’s responsibility is to turn off those polarized T helper cells so that other T cells can carry out their duties and eradicate pathogens or cancer. And Treg do it in an epitope-specific way, as we already mentioned.
Because of this, it is more crucial to find an epitope that could activate polarized T helper cells rather than any cancer – or pathogen-specific self-elements.
To make matters even more challenging, one might wonder how Tregs can shut down polarized T helper cells that are nonself-specific if they are self – specific and act epitope specific. It’s possible because Tregs are cross-reactive and can only inhibit polarized T helper cells that have TCR-specificity in common.
In other words, managing one’s self-tolerance and managing an effective anti-nonself response are the same thing. In addition, & nbsp,
Together, these three papers offer a thorough analysis of the SPIRAL model we created to explain how receptors function in an adaptive immune system:
The” Hygiene hypothesis” may be supported by concurrent cross-reactivity of microbiota-derived epitopes to both self and pathogens.
Could Foxp3 + regulatory T cell precursors be saved from thymic deletion by cross-reactivity? & nbsp,
Foxp3 + Regulatory T Cells in the Microbiota Could Manage Pathological T Helper Responses
the & nbsp,,