A bug about the positive selection of T cell differentitation

[*******]

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Hey guys, i came up with a question when studying Immunology. I have asked my professor,but he just,u know,said something ambiguous and walked through it.
Here is my question

It is already known that T cells need go through positive and negative selection,so that they can develop into mature T cell; In positive selection , TCR in the surface of T cell need to recognise and combine the Antigen peptide-MHC complex from the thymic epithelium to a medium extent , and in negative selection those recogising Self-Antigen peptide-MHC complex will turn into apoptpsis .
We should take notice that thymic epithelium could almost express all self-antigen peptide in our body. So in this way ,every T cell or TCR, which passes the positive selection,should recognise and combine at least one kind of self-Antigen peptide-MHC complex,because of the rule of positive selection.
Then, how could this T cell pass negative selection? There is at least one kind of self-pMHC existing for every T cell!

 

[*******]

the point is the peptide given by thymic epithelium in positive selection! my professor told us ,'the atigen peptide in positive selection is some kinds of self peptide ,u can find it in other places of our body.That's not a special peptide.'

 

[threepwood]

If I’m understanding your question correctly, you’re wondering how auto-reactive T-cells are filtered out when thymic cells are presenting self-antigen during both positive and negative selection.

Answer: Successful selection is attributable to finding the sweet spot of MHC-peptide binding strength by the T-cell. If it binds weakly, it survives positive selection, because the weak binding means it can bind MHC molecules but does not bind so strongly that it will auto-react. If it binds strongly, it fails negative selection because it could lead to auto-immunity. Thus, it’s ok to have self-peptide presented by the thymic cells. My professor compared this process to Goldilocks.

Could be wrong but that’s my understanding!

 

[pn1924]

Sorry about being so late to the party, and this may be way beyond what you need for med school. There are actually two positive selections, the first happens in one place, the second happens in another place after negative selection.
first positive happens at thymic epithelium [thymic cortx] and in it you get 4 days to bind to an MHC, if not fox activates apoptosis.
then onto thymic medulla for negative selection [so they occur in physically distinct places]
then stay in medulla for positive two - do you prefer MHC I (become Ttoxic) more or MHC II (become Thelper)