Tumor cells express foreign antigen in the context of class I MHC. It is recognized as non-self and get killed. DCs present in the context of class II. Different signal cascade and different kind of protein release. Read more on immune reponse and class restriction.

Its play of self and non-self recognition mechanism.

I am much delighted with your response to my question ,, i am thankful to you for sparing your valuable time to my queries ,, i am not sure whether i have convey my queries properly or not ,,

But I got some satisfied answer to the below question ,, thanks a lot ,,

DC present tumor antigenic peptide via MHC Class II to CD4+ T cells, and activate CD4+ T cell which in turn secrete cytokines like IFNg ,TNF alpha, etc which kills tumor cells ,that has the abnormal expression of the protein matching to the peptide presented by DC ,

why this cytokine is not killing DC cell that carries tumor antigenic peptide ?,,

for more detail of killing performed by T-cell,u can read for KIR(KILLING RECEPTOR ) pathway,which helps the T-cell in taking decision for killing any cell.

Is lupus a result of dendritic apoptosis?

Sarah dear... no lupus is different... it is a autoimmune disease of that kind where antibodies strikes on special body tissues or cells like heart cells and thyroid tissue cells

I think this is a very good question. I believe it has to do with T cells changing their homing pattern once primed by dendritic cells. So instead of going to the lymph nodes to check out what yummy antigens dendritic cells have to offer they now home to the peripheral tissue where the antigen was first captured.

Mr Suresh.... CD4+ cells secrete cytokines on recognition with the antigenic peptide on dendritic cells or macrophages (or any APC), they activate other T and B cells but never kills the APC (exogenous pathway). CD8+ cells or the T-cytotoxic cells can recognize Ag complexed with Class I MHC (endogenous pathway) and release pore forming enzymes, thus destroying the APC that presents the foreign Ag irrespective of what APC it is, including dendritic cell.

Interesting responses. It could explain some aspects of APC-T cell interaction, however, I'm still not clear how APC's cross presenting viral antigens are not killed by CTLs. Imagine two situations below:

The first situation: You have a virally infected dendritic cell. Viral antigens are processed and presented on MHC-I for CD8+ T cell recognition. Since this cell is infected, it should be killed by CD8+ T cells. This makes sense immunologically.

The second situation: Consider that APCs (lets say dendritic cell more specifically) phagocytose virally infected and/or dead cells. In this case, antigens will be presented mainly on MHC-II for CD4+ T cell recognition. CD4+ T cells don't generally have cytotoxic features. However, dendritic cells can cross-present this kind of extracellular antigens on MHC-I proteins to activate CD8+ T cell responses. In this scenario, do CD8+ T cells kill the APCs innocently doing their job?

How can a CD8+ T cell make the distinction between two scenarios? It makes sense to kill APCs in the first scenario, but not the second scenario. Can anyone provide some insight?

From below statement, I assume that the Tumor antigen presenting Dendritic cell is also killed.Only when it is in interacting zone.

(vicinity of Th cell and APC).

The TH cell, a major producer ofcytokines, close cellular interaction occurs when the T-cell receptor recognizes an antigen-MHC complex on an appropriateantigen-presenting cell, such as a macrophage, dendritic cell, or B lymphocyte.Cytokines secreted at the junction of these interacting cells reach high enough local concentrations to affect the target APC but not more distant cells. In addition, the half-life of cytokines in the bloodstream or other extracellular fluids into which they are secreted is usually very short, ensuring that they act for only a limited period of time

and thus over a short distance.

Reference -Cytokines CHAPTER 12 281 -Immunology Janis Kuby.

I am satisfied with the answer , which ruins me for long days.

Plz give your comments ,if you are not satisfied with it ..

Dendritic cells present antigens in the context of both MHC I and II to Th and Tc cells. Antigen presenting DCs mainly are located in secondary lymphoid organs and present antigens to naive T cells and after activation these primed T cells migrate from secondary lymphoid organs to peripheral tissues to do their jobs like killing infected or transformed cells.

Dear All,

The problem is not obvious to me, and I would not trust textbooks, though they are very cool.

I do believe there is some killing of APCs, and I could suggest this paper to support it :

CD4+ T Cells Can Protect APC from CTL-Mediated Elimination

http://www.jimmunol.org/content/176/12/7379.full

Another thing to take into account is that it seems that the APCs presenting to CD4 and CD8 in lymph nodes might not be the same ones (at least in the first phase), see

Robust Anti-viral Immunity Requires Multiple Distinct T Cell-Dendritic Cell Interactions

http://www.cell.com/cell/abstract/S0092-8674%2815%2900980-0

Best,

Could potentially be due to the CD8 T cell recognizing the self MHC I molecule on the DC that prevents it from being killed. Interesting question though!

The presentation of antigens on the cell surface is done by two different molecule complexes: The MHCI and the MHCII complexes. These are coupled to different pathways and are recognized by different T cell populations.

The MHCI molecule presents all proteins which are present in the cell on the surface. To do so, peptides coming from the proteasome (where long proteins are digested) are transported in the the endoplasmatic reticulum (ER) by a special transporter called Transporter associated with Antigen Processing (TAP). By doing so, a profile of all proteins expressed in the cell is presented on its surface, including proteins which arise due to an infection of the cell. MHCI is recognized by cytotoxic (or CD8 positive) T cells which subsequently kill all cells which show foreign antigens on their surface (since this is a sign for an infection).

The MHCII complex only presents proteins on its surface which have been taken up by phagocytosis (so here only external proteins are presented). To prevent binding of cellular proteins in the ER (like for MHCI), the binding pocket of the receptor is blocked by the invariant chain. This chain dissociates only when the MHCII complex enter the phagolysosome with its acidic conditions. This makes sure that only proteins which have been taken up by phagocytosis are presented. MHCII complexes are recognized by helper (or CD4 positive) T cells, which in turn can activate B cells to raise a proper immune response.

In theory this should prevent all problems. In the practical life this is different for dendritic cells in a mechanism called "cross presentation". In this mechanism antigens which are taken up by phagocytosis are exported from the phagolysosme and imported into the ER. This pathway also involves the TAP protein. By choosing this way, APC can activate naive CTL which will kill all cells which present this antigen. See references 1 and 2 for more details.

This pathway is important for the immune response to a number of viruses as well as tumors which evade the MHCII mediated immune response by suppressing the MHCII antigen presentation. See references 3 and 4.

It is also important for the stability of the self-tolerance by the deletion of auto-reactive CTL. See reference 5 for details.

regards

Follow this link is very helpful

https://biology.stackexchange.com/questions/24220/why-cytotoxic-t-cells-dont-kill-dendritic-cells-when-they-present-antigen

Regards

Without doing a through research, I'd like to speculate.

According to literatures, Naive T cells get activated in lymph nodes. By then, they still express homing markers like CCR7 and CD62L. They don't have much cytotoxicity.

During activation rendered differentiation, they lose those markers and leaves the lymph nodes for the circulation. Meanwhile, they gain cytotoxicity.

I'm not sure if by then they will kill the DC's presenting the same antigens.

Professional APC can avoid from being killed by CD8 because it is mainly located in lymph node where there are only naive and central memory CD8 which has much less effector function. However, what about non-professional APC? They are located at peripheral tissues where effector and effector memory CD8 T cells are also there.

This would be helpful for those interested in the question to consider the paper "Programmed Cell Death of Dendritic Cells in Immune Regulation" Article Programmed Cell Death of Dendritic Cells in Immune Regulation

Might be also because of DCs presenting ag expresse highly B7 which binds CTLA-4 on T cells? Sergei Pustylnikov

Francesca Costabile there are many ways to interact between DCs and T cells. Seems that CD80/CD86 interaction of DCs with CD28 or CTLA4 of the T cells is not related to DC killing http://www.jbc.org/content/289/11/7747.short However, this interaction probably can help them to contact via CD8-TCR.

Sergei Pustylnikov look what Janeway's Immunobiology says on this topic: " Another receptor for B7 molecules is CTLA-4 (CD152), which is related in sequence to CD28. CTLA-4 binds B7 molecules about 20 times more avidly than CD28, but its e fect is to inhibit, rather than activate, the T cell. CTLA-4 does not contain an ITIM motif, and it is suggested to inhibit T-cell activation by competing with CD28 for interaction with B7 molecules expressed by antigen-presenting cells. Activation of naive T cells induces the surface expression of CTLA-4, making activated T cells less sensitive than naive T cells to stimulation by the antigen-presenting cell, thereby restricting IL-2 production"

I would conclude that CD80/CTLA-4 interaction is crucial in limiting excessive T cells activity during contact with APC. Also, it's good to remember that activated T cells no longer need co-stimulatory molecules. Thus, APCs provide a balanced signal to activate T cells at the same time protecting themselves from killing via inhibitory pathway. Once T cell is detached it can exhibit cytotoxic activity only in the presence of Ag-MHC I.

Here's couple links explaining this:

1. Allison himself talks about the role of CTLA-4: Article Fundamental Mechanisms of Immune Checkpoint Blockade Therapy

2. Clear explanation of what happens (see Figures 1&2): Article CTLA-4 and PD-1 Control of T-Cell Motility and Migration: Im...

Briefly, CTLA-4 is expressed shortly after T cell activation and serves to protect APCs (and everything else where it is expressed) from excessive T cell activation and proliferation. Also CTLA-4 makes T cell detach from APC and travel to where it's action is needed - into inflammatory sites.

Pavel Nesmiyanov this is a nice point. It underlines that for DCs expression of CD80 might not only be important for co-stimulation but as well, for survival. Thanks for the links!

@Noha Afifi could you please provide some references for that?

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2905219/

Effector CTL kill DCs but memory CD8+ Tcells protecy them from killing by stimulating the production of granzyme binhibitor

@Noha Afifi, thank you. I guess the question was on naive T cell activation during primary response, but your answer adds to that.

https://www.nature.com/articles/s41467-020-18570-x

Please read this article

B7-H1 maintains the polyclonal T cell response by protecting dendritic cells from cytotoxic T lymphocyte destruction