How does a T-helper cell know which micro-organism (bacteria, virus, allergen) it is after binding with the MHC complex of an antigen-presenting cell?

Answer

Dear Wim,

In our body a whole bunch of T helper cells are made (just like a whole bunch of B cells) over and over again. These T-helper cells each get a T-cell receptor on their membrane (or rather the gene for it expressed in their DNA). As with the antibody gene in the B cells, this T-cell receptor gene is put together during cell differentiation into T-helper cells (puzzling pieces of DNA together, similar to cutting and pasting for genetic manipulation, but now in vivo) . The TCR that each T cell obtains is therefore different: they can all bind to one of the MHC protein complexes, but that is insufficient for activation of the T cell. The T-cell only gets going (will only clone and produce and secrete cytokines) if, in addition to this MHC binding, also a binding (or better a number of weak bonds) can be made with what is presented by the MHC. In addition, the T-cell in question has been pre-screened to ensure that it does not respond to endogenous material (MHC complexes themselves, or anything that can be presented on them that is endogenous). After all, T cells that would respond to this could give rise to autoimmune responses, they (it is believed) go into apoptosis the moment they find and bind body’s own material, presented on MHC). Only T helper cells that bind with a) one of the MHCII complexes (MHCI is for cytotoxic T cells), b) something presented on this MHCII that is not self-reactive: clone and secrete cytokines to stimulate the immune response (e.g. via antibodies, but also non-specific) to start up and increase. To distinguish between MHCI and MHCII complexes, T-helper and on the other hand, cytotoxic T cells have a helper receptor (CD4/CD8, respectively). Helper T cells react to foreign material that white blood cells have picked up via endocytosis: only these things end up as fragment (peptide) on the MHCII complexes. MHCI complexes present fragments of material that was or is present in the cytoplasm, possibly also foreign to the body: for example, virus proteins, made by the ribosomes of the infected cell or ‘cancer’ proteins (mutated and therefore foreign to the T cells), also made on the ribosomes of the mutated cancer cell.

B and T cells do not so much recognize what they bind, or where it comes from, they rather recognize ‘how’ they are presented with this: on MHCI complexes (cytotoxic T-cell springs into action and kills the cell that shows that she has something foreign in her cytoplasm), on MHCII (helper T cell emits signals (cytokines) to show that a WBC is picking up things that are not normal), or free foreign antigens, not presented on MHC complexes, captured by the membrane-found antibodies or also called B-cell receptors by analogy with the TCR.

sufficient as an answer?

kind regards,