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In my immunology notes, it states that B lymphocytes (and other APCs) capture and present antigens to T lymphocytes that is specific for an antigen, but that the T cells do not necessarily recognise the same epitope. How can a cell be specific to an antigen but not to the epitope presenting on the surface of the antigen?

I've been in the process of discussing this with a friend and trying to make sense of Janeway's immunobiology and we've come to the theory that the APC recognises the antigen and takes it up, breaks it down and presents the epitope via the MHC where it is then recognised by the T cell. Am I right in saying that the antigen is broken down into many fragments that act as epitopes but each clonal expansion of T cells can only recognise the various epitopes of one antigen?

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    $\begingroup$ It's mainly because antigens have multiple epitopes, and so the T/B cells will recognize one epitope, but you'll get multiple cells recognizing multiple epitopes. The polyclonal expansion of these cells allow the attack to come at multiple angles of the same antigen at once. $\endgroup$
    – CKM
    May 30, 2016 at 14:52
  • $\begingroup$ Okay, I think I understand why T/B cells can bind multiple epitopes but I'm still confused about how this leads to them being specific to one antigen, as surely, different antigens could have the same epitopes on them? Or is each type of epitope only found on one antigen? Thanks for your help! @CMosychuk $\endgroup$
    – Elizabeth
    May 30, 2016 at 15:04
  • $\begingroup$ Take a look at the following image. The shapes on the bacteriums surface are the antigenic determinants, aka the epitopes. Notice how they can differ: each antigen has many epitopes at once. $\endgroup$
    – CKM
    May 31, 2016 at 13:22
  • $\begingroup$ Thanks for the image, it really helps me to visualise it. I think my confusion is coming from the fact that on my midterm (will edit the post and tag homework, I read the rules after posting) it says that "Concerning T lymphocyte/B lymphocyte co-operation in humoral immune responses to T dependent antigens: The epitope recognised by the T cells and B cells must be identical (FALSE) The antigen recognised by the T cells and B cells must be identical. (TRUE)" And it's the second statement that's confusing me. I don't understand that bit, does that make sense? @CMosychuk $\endgroup$
    – Elizabeth
    May 31, 2016 at 20:01
  • $\begingroup$ "...it states that B lymphocytes (and other APCs) capture and present antigens to T lymphocytes that is specific for an antigen" - Shouldn't it read"...present epitopes to T lymphocytes..." or "...present peptides" (that's what they are? Which leads to: Do presented peptides have/include epitopes, or: embed one and only one epitope). - Ref. @CMosychuk – Elizabeth May 30 '16: Do you mean: if B-Cells "edit" one and the same antibody they are specific for, they are being "activated" from different sides (even different strains of virus causing that activation)? $\endgroup$
    – Peter Bernhard
    Apr 30, 2021 at 17:16

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Perhaps it would simplify for you to think of a model system? Let's take HIV because it's simple. The antigen in this case is a protein called ENV and it looks like this.

enter image description here

All of those arrows are pointing "regions" of the antigen that an antibody will bind to. Since the B cell makes the antibody you can think of these regions as where the B cell will bind to. They call these regions epitopes.

Do you see how there are many different sites on one antigen? Well one of those epitopes can be for a B cell and one of those epitopes, which can even be on the other side of the antigen, can be an eptiope for a T cell. So while T and B cells recognize the same antigen, in this case HIV Env, they needn't bind the same epitopes.

I think where you may be getting confused is when B cells chew up an antigen, the epitope they display on MHCII and display to T cells is not necessarily the same epitope it used to recognize the antigen. The B cell chews up the entire antigen, including T cell epitopes, and displays them on MHCII.

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  • $\begingroup$ I think it's worth mentioning in that context that B cells only produce antibodies that refer to the epitope they recognize, not the ones they present to T helper cells (as I feel rather insecure about that...). $\endgroup$
    – Peter Bernhard
    Apr 30, 2021 at 16:55
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For this answer lets restrict ourselves to T dependent MHC II mediated responses.

So, an APC like a macrophage or a dendritic cell, takes in a pathogen by phagocytosis and degrades it inside the cell. Some of its broken proteins, which are antigens are presented on the MHC II of this particular APC.

The B cells also do something similar but they identify either free floating antigens or the ones that are expressed by phagocytic APCs. These antigens are broken down in the lysosome. These fragments now are expressed on the surface along with MHC II. This fragment may or may not contain the epitope that the B cell receptor (surface antibody) originally recognised the antigen with. Also, it is not that just one of the fragment is taken to the surface, most of them make it, each with a separate MHC.

The T cell that is going to now interact with this B cell may have a TCR (T cell Receptor) against the epitope in any one of those fragmented antigens on the MHC.

This T-cell is specific to that particular epitope of the antigen it bound to, similarly there could be another T-cell that could recognise some other fragment of the same antigen brought to the membrane by a different MHC II.

So, the epitope that the B-cell and the T-cell recognised the antigen with, needn't be the same. But logically, there's a possibility that they may be.

enter image description here

Note that:

  1. The processing of antigen in the phagocytic APC is not shown in the picture.
  2. B cell recognises antigens not that are displayed on the MHC II (this the T cell does) but those that are tethered on the APC membrane.

Image: Nature Reviews Immunology.

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  • $\begingroup$ "The B cells (...) identify either free floating antigens or the ones that are expressed by phagocytic APCs." - 1. True that B cells do not take up whole viruses? 2. Any basic textbook reference for APC presenting, then B taking up? 3. Still true that cytotoxic T cells do not uptake, in contrast to B cells(!)? $\endgroup$
    – Peter Bernhard
    Apr 30, 2021 at 16:48

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