T Cell Development

[shellybirdy]

good work here

[andrewzds]

thank you so much 4 the video!!!

[xtremetom180]

some really good stuff here

[Mephalay]

Allahın işine bak.

[RonB0105]

This is an excellent video!!!!

[tsf2ba]

great video...:)

[Kontotification]

I thought the positive selection was made in the cortical area and the negative in the medullar. Seems like this video is confusing at least me for a bit there in the end.

[dsk0189]

If only lectures were this clear and simple :) thank you so much

[jesuistahmid]

ahh wish it talked more about the VDJ recombination

[Wimzig]

@jesuistahmid The T cell receptor (TCR) consists of a beta-chain and an alpha-chain, both with variable regions that specify which peptide/MHC complex the receptor will bind. In the thymus, beta-chain rearrangement occurs before alpha-chain rearrangement. Beta-chain gene configuration consists of "variable (V)", "diversity (D)" and "junctional (J)" gene segments. Rearrangement of all of these contributes to the specificity of the variable region of the TCR.

[Wimzig]

@Wimzig First, there is a random loss of D and J segments so that the junction between the two segments is also random (e.g. if you have D segments 1 to 27 next to J segments 1-6, D segments 19-27 and J segments 1-4 might be randomly lost, leaving D18 next to J5). Next, there is random loss of some of the V segments, again giving a random arrangement of segments at junctions ("junctional diversity").

[Wimzig]

@Wimzig The random V segments you're left with encode two of the complementarity determining regions (CDR - these are the areas on the part of the TCR that define which peptide/MHC complexes it can recognise) on the variable region of the beta chain of the TCR. The third CDR is defined by the junctional diversity at VDJ junctions. CDR3 is the most variable CDR in TCRs and makes the major contact with the peptide in the MHC groove. Alpha-chain rearrangement follows beta-chain rearrangement.

[Wimzig]

@Wimzig Before alpha-chain rearrangement, both CD4 and CD8 are expressed on the T cell surface with a surrogate alpha-chain allowing the TCR to function. Positive selection already acts here and continues as alpha-chain rearrangement occurs. The alpha-chain gene conformation does not consist of any D segments and the rearrangement results in junctional diversity only between V and J segments. The rearranged alpha-chain replaces the surrogate if it passes positive selection. Hope that helps!

[Atena212]

I don't understand very well negative selection..

[uterina]

@Atena212 Negative selection is the process in which thymocytes whose TCRs bind strongly to self peptide antigens in association with self MHC molecules are deleted. This eliminates developing T cells that are strongly autoreactive against self antigens that are present at high concentrations in the thymus. The net result of these selection processes is that the repertoire of mature T cells that leaves the thymus is self MHC restricted and tolerant to many self antigens (Abbas et al, 6th ed.)

[WatchOut20Me]

@Atena212 Negative selection occurs in 3 scenarios:

1)Some TcR are abnormal (due to faulty rearrangement).

2)Resulting TcR is unable to interact with any HLA molecule.

3)small percentage die due to a strong interaction with the HLA peptide complex. The peptide in the complex is self antigen so strong interaction with the HLA peptide complex will signal cell death ---> tolerance to self antigens.

Hope this helps

[joao977]

@WatchOut20Me Exactly^^

[Wimzig]

@WatchOut20Me I don't think a lack of interaction with HLA is strictly speaking "negative selection", rather it's just "death by neglect". Negative selection (or central tolerance, as stated in the video), is an active process to remove T cells with TCRs that have too high affinity (though I'm not sure about avidity, as the video says it is) for HLA(MHC)/self peptide complexes.

[zidane408]

really wonderful

thank you very much

I'm a pharmacist from Egypt

in 5th year of the faculty

wish you come here and see Pyramids

[spontaneousbaba]

Thankyou for uploading......thats very nice of you...

[Sublett22]

Thank you, much appreciated.