Peripheral T Helpers

[dyspareunia]

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This is from an RX question (qid 2417).

Basically the question asks whether or not a peripheral T helper in presence of MHC2 bound antigen, but the absence of the second signal will be able to perform effector functions.

I understand that immature cells need the second signal or they'll go into anergy, but how do I know that "peripheral T helper lymphocyte" means a mature naive T helper and not an effector T helper? I incorrectly assumed that "peripheral T helper" implied an effector cell, which doesn't need the second signal to carry out functions.

 

[Apoplexy__]

I don't have Rx so I can't see the question, but here's my answer as I understand the topic:
-Co-activation of T cells with an APC (that is, both the T cell and APC "benefit") only occurs in a T cell - APC interaction. T cell effectors, which are already activated themselves, just go around activating other cells and don't need to be activated.
-Therefore, when asked if a T cell needs a second signal to perform functions, it can only be referring to the co-activation between a T cell and an APC.
-I can't think of any way you would know that "peripheral T helper lymphocyte" meant a mature naive vs. effector.

 

[dyspareunia]

I don't have Rx so I can't see the question, but here's my answer as I understand the topic:
-Co-activation of T cells with an APC (that is, both the T cell and APC "benefit") only occurs in a T cell - APC interaction. T cell effectors, which are already activated themselves, just go around activating other cells and don't need to be activated.
-Therefore, when asked if a T cell needs a second signal to perform functions, it can only be referring to the co-activation between a T cell and an APC.
-I can't think of any way you would know that "peripheral T helper lymphocyte" meant a mature naive vs. effector.

Are you saying that effector T helpers don't interact with APCs?

So I don't know if this is too much info, but I'm sure a mod will delete it if it is.

A peripheral t helper lymphocyte engages a MHC2+peptide on an APC. No other contact is made between T cell and APC. Which of the following can be concluded?

A. T lymphocyte will be activated and fully able to perform effector functions
B. T lymphocyte will undergo anergy

 

[Apoplexy__]

I think a general overview will help clarify this topic:

There are two types of APC activation: Co-activation with a CD4+ T cell (naive) and singular activation by an effector T cell (activated).
-Co-activation: This is the typical thing you're well aware of, the two-step activation of B7-CD28, and MHCI/II - TCR. Both the APC and T cell are activated.

-Singular activation: CD40L is a very special ligand on T cells that only appears when they are activated. Therefore, the CD40L-CD40 interaction only occurs between an activated T cell and an inactive APC. This activation has 2 steps also:
Step 1 for macrophages and CD8+ cells = IFN-gamma (Step 1 for B cells = MHCII-TCR)
Step 2: CD40L-CD40 interaction
Notice that some APC's don't have the MHC-TCR interaction as part of their activation. This is because MHC-TCR binding only serves them the purpose of letting the T cell know that they're the ones that should be activated. The MHC on the surface of these APC's doesn't have a biochemical signal cascade behind it when recognized by an effector T cell.

In contrast, there's only one type of T cell activation: Co-activation with an APC. Simple. Therefore, when the Rx question asked about a 2-step T cell activation, it could only have been referring to the activation of a naive T cell with an APC.

As an aside, the only other complicating element is that B cells can be singularly activated through T cell-independent activation. This is just where some lipid or polysaccharide antigen cross-links the surface IgM. There was no affinity maturation to optimize this binding, it's more of a priming proliferative signal. LPS can do this to B cells too. If the B cell is activated through this way, it still can't class switch until it's been activated through the power of CD40L.