Role of T Cells in the Immune Response

The immune response results from a cellular collaboration between Antigen Presenting Cells (APC), Tcells and B cells.

It has been established that CD4+ lymphocytes (helper T cells) are immune response mediators, and play an important role in initiating and maximising the adaptive immune response. These cells have no direct cytotoxic or phagocytic activity; and cannot kill infected cells or clear pathogens. They rather manage the immune response, by directing other cells to perform these tasks.

When a foreign protein is injected in the organism, it is captured by APCs via an endocytosis mechanism, fragmented into peptides and presented to helper T-Cells via class II MHC (Major Histocompatibility Complex class II). Helper T cells express T-cell receptors (TCR) that bind specific antigens (T epitopes) bound to Class II MHC molecules. The activation of a naive helper T cell causes the release of cytokines, which influences the activity of many cell types, including the APCs that activated it. In particular, helper T cells can promote the maturation of B cells into Plasma cells, which secrete high-affinity IgGs directed against the foreign protein. Plasma Cells, IgG secreting cells, are short-lived (2-3 days). These IgG antibodies bind antigens, flagging them as targets for phagocytes, and trigger the complement cascade. About 10% of plasma cells will survive to become long-lived, antigen-specific cells called memory B cells. Being already primed to produce specific antibodies, these cells can be called upon to respond quickly if the same pathogen reinfects the host by presenting the specific epitope to T cells. Moreover, when the foreign protein is administered repeatedly in the time (such as for therapeutic proteins), the immune response can be amplified at each new administration and finally lead to inflammation. Therefore, the presence in a therapeutic protein of T epitopes that can stimulate T cells is an essential factor for the immunogenicity of the protein. Accordingly, it has been established that eliminating these T epitopes in a therapeutic protein significantly reduces the humoral response against this protein.