What determines whether a regulatory T cell suppresses a naive T cell binding the same antigen-presenting cell?

Question

Here's what I learned about how regulatory T cells work:

There is a self-recognising naive T cell around.

A regulatory T cell that recognises the same self-antigen binds the same antigen-presenting cell as one of these T cells.

It suppresses activation of the naive T cell.

However, let's say the antigen-presenting cell is presenting foreign antigen on some of its MHC molecules. The naive T cell binds the antigen and there happens to be a regulatory T cell nearby binding a self-antigen on the same antigen-presenting cell.

Does the regulatory T cell suppress the naive T cell? Is it just do with proximity, or do both cells have to bind the exact same antigen?

Answer 1

There a strong implication for a feedback loop mechanism for IL-2.

If a Treg is bound to an APC, it downregulates IL-2. It will then require exogenous IL-2 to be maintained. This IL-2 comes from a nearby naive T cell which is also binding a self-antigen. When that happens it upregulated IL-2. When it upregulates IL-2 and dumps it to all nearby cells which are then taken up by the nearby Treg. That causes Treg to continue its normal function by suppressing all nearby cells. It's an IL-2 negative feedback loop. It's all about proximity. What you are suggesting is not feasible since T cells recognise APC cells by MHC class II which are loaded by phagocytosis, meaning that the self-antigen has to be taken from outside of the cell. That means the APC would have to engulf two different self-antigens and displayed them on separate MHC class II which I guess is probably possible...

Check out this paper and figure 2:

http://www.cell.com/cell/pdf/S0092-8674(08)00624-7.pdf