RBCs as antigen-presenting cells?

Thought you were beginning to understand how human immune systems worked? Ever consider the role of erythrocytes/RBCs as antigen-presenting cells?

https://medicalxpress.com/news/2020-07-vaccines-blood.html

I'll try to check back, but I can't promise to stay active. I'm busy with other problems.

For those who don't know, I live in Florida, which just passed many nations in COVID-19 cases. Heck, Orange County alone has far more cases than the entire continent of Australia, which freaked out when they had a mere 318 cases in a day.

Did I mention that we just reopened Disney World?

Moderator note: posts discussing covid-19 have been moved to Coronavirus - worldwide spread and control

 

Does anyone with less pressing concerns know of any other research on the idea that human erythrocytes/RBCs can act as antigen-presenting cells without being eaten by phagocytes?

 

It is not that red cells act as antigen presenting cells but, as the citation says, that they can carry antigen and pass it to antigen presenting cells in spleen. We have known about this for maybe fifty years. The red cells pick up antigen in association with complement via the complement receptor CR1. They then pass through the spleen where the complexes are 'wiped off' and taken up by APCs. I believe this used to be called 'pitting' of red cells. Red cells are the main bulk system for clearing circulating antigen-antibody complexes.

 

This is not an antigen-antibody complex, but only the antigen, and I'm pretty sure you don't count T-cells as antigen-presenting cells. If it depended on preexisting antibodies, that would defeat the purpose of immunization.

If I read current research correctly, RBCs are passing virions as antigens directly to T-cells, which then activate phagocytes. Because of their direct interaction they need epitopes that act as "don't-eat-me signals". Here's where the term antigen-presenting came from. The title is
Erythrocyte-driven immunization via biomimicry of their natural antigen-presenting function
and two groups at Harvard appear to think this is based on relatively recent discoveries. Perhaps you should contact the editor, Chad A. Mirkin.

 

Abstract from the citation above.
Erythrocytes naturally capture certain bacterial pathogens in circulation, kill them through oxidative stress, and present them to the antigen-presenting cells (APCs) in the spleen. By leveraging this innate immune function of erythrocytes, we developed erythrocyte-driven immune targeting (EDIT), which presents nanoparticles from the surface of erythrocytes to the APCs in the spleen. Antigenic nanoparticles were adsorbed on the erythrocyte surface. By engineering the number density of adsorbed nanoparticles, (i.e., the number of nanoparticles loaded per erythrocyte), they were predominantly delivered to the spleen rather than lungs, which is conventionally the target of erythrocyte-mediated delivery systems. Presentation of erythrocyte-delivered nanoparticles to the spleen led to improved antibody response against the antigen, higher central memory T cell response, and lower regulatory T cell response, compared with controls. Enhanced immune response slowed down tumor progression in a prophylaxis model. These findings suggest that EDIT is an effective strategy to enhance systemic immunity.


An awful lot of immunology presented in papers these days is muddled. I haven't read this paper in full but I would make the following comments on the abstract.

1. The bit about red cells killing bacteria through oxidative stress sounds like bullshit to me and does not seem relevant to the mechanism of the treatment described.
2. What seems clear is that they are putting some stuff on the surface of red cells and getting the stuff taken by the red cells to antigen-presenting cells in the spleen. Those antigen presenting cells will be either MHCII expressing macrophages and interdigitating dendritic cells or they will be follicular dendritic cells. The mode of antigen presentation is completely different for the two, the second involving complement. I suspect they are talking about interdigitating dendritic cells - the classical 'professional APCs'.
3. Red cells normally 'present' surface material to splenic cells that has been acquired through association with antibody, complement and CR1 binding. However, when the splenic cells 'pit' red cells they can be expected to pick up anything on the red cell surface that they find sticky. Since about the 1960s pitting has been seen as a general mechanism for 'cleaning' red cells. It sounds to me as if they are just making use of that and it has nothing to do with their first sentence or any particularly new discovery.
4. They are clearly implying that the APCs in the spleen that take the antigen from red cells then, as a second step, present material to T cells. This would be as peptide fragments rather than as whole antigen.

Dependance on pre-existing antibody does not defeat the purpose of immunisation. Immunisation depends on some form of antigen specific recognition to get it going. Otherwise the antigen would just be ignored. The standard theory says that antigen is bound by low affinity/broad specificity 'natural' antibody most of which is IgM. We all have antibody to everything all the time, just not enough to kill an actively invading organism. So immunisation is a process of antibody amplification and refinement, not starting from scratch. The CR1 on red cells is there to bing antigen that has either been picked up by low affinity IgM, which is a good complement fixer, or by complement directly through sugar residues such as mannose or other innate complement engaging pathways.

I have not heard this story of red cells picking up bacteria but if they had the chance to in the face of the shear forces in blood the interaction would probably involve complement binding to bacterial surface sugar residues - at which complement is very good. Immunology labs used to use a yeast called zymosan to activate the alternative pathway of complement. The complement would then bind CR1 as before.

I don't see any indication that red cells pass antigen to T cells directly. T cells do not have any whole-antigen bdingin capabilities. They only respond to peptide fragments presented with MHC.