Understanding T Cells: T Cell Types, the T Cell Receptor and T Cell Activation, Differentiation and Functions

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When a pathogen enters the body, it is first met by the innate immune response. This is a non-specific response that identifies pathogens from the presence of general microbial-associated molecular patterns (MAMPs). In addition to acting as the first line of defense, the innate immune system also activates the adaptive immune response. The adaptive immune response is made up of cellular and humoral immunity and relies on the recognition of specific pathogen signatures called antigens to remove threats.

This article focuses on cellular immunity and the T cells that comprise it. We discuss the different types of T cells, their development and the consequences of defective T cells.

What are T cells??

T cells, also known as T lymphocytes, are the immune cells that drive the cellular immune response. There are several different types of T cells, each playing a distinct role. The functions of T cells include killing pathogens and damaged cells, moderating the immune response and facilitating the actions of other immune cells.?

T cells are distinguished by the presence of the T-cell receptor and the cluster of differentiation 3 (CD3), which are found on all T cells, regardless of their role. T cells can further be categorized into subtypes by the expression of other markers including CD4and CD8.

Following the identification of B cells in the 1950s, research by Jacques Miller in the early 1960s showed that the removal of an organ called the thymus in mice resulted in severe immunodeficiencies. However, it was not until the late 1960s that lymphocytes produced by the thymus were designated as “T cells” and were seen to facilitate the production of antibodies by B cells.

Since then, T cells have been studied in depth, and we now have a thorough understanding of their subtypes, development, functions and interactions with antigens. Even so, rare types and functions of T cells are still being discovered.

What do T cells do?

Like other lymphocyte cells, T cells begin development in the bone marrow as hematopoietic stem cells (Figure 1). However, while B cells and natural killer (NK) cells typically remain in the bone marrow until they are fully mature, immature T cells – known as thymocytes – leave the bone marrow and travel to the thymus to mature there. Once fully mature, T cells leave the thymus and enter peripheral circulation. By entering circulation and residing in immune organs such as lymph nodes, T cells increase their chances of encountering the specific antigen that will activate them.

T cells cannot interact directly with pathogens. The pathogens must be processed into short peptide chains called antigens inside cells and presented to the T cells on major histocompatibility complexes (MHCs). The interaction of MHC–antigen combinations with T-cell receptors (TCRs) activates the T cell and initiates its effector functions. Activated T cells proliferate rapidly, producing thousands of clones that all target cells expressing the same antigen. T-cell effector functions include:

• Directing and managing other arms of the immune response
• Directly killing infected or damaged cells
• Downregulating the immune response once the infection is cleared

Types of T cells

There are several different types of T cells, all of which play an important role in the adaptive immune response. T cells are categorized according to the markers on their surface, the structure of their T-cell receptor and their effector functions (Figure 1).

The two main types of effector T cells are:

• CD4+ T cells, also known as “helper” cells
• CD8+ T cells, also known as cytotoxic T lymphocytes (CTLs) or “killer” T cells

Helper T (Th) cells direct and facilitate the immune response, while CTLs target and destroy infected and damaged cells. Regulatory T cells (Tregs), which are a subtype of CD4+ T cells, suppress and regulate the cellular immune response. Finally, memory T cells are antigen-specific cells (either CD4+ or CD8+), which survive for long periods following the clearance of infection or damage and are able to proliferate rapidly to produce large numbers of effector cells, if that specific antigen is ever encountered again.?

The presence of CD4 or CD8 on Th cells or CTLs determines what kind of antigen will activate the cell. TCRs on CD4+ Th cells interact with MHC class II molecules on professional antigen-presenting cells (APCs) loaded with antigens from extracellular sources such as bacteria or parasites. In comparison, CD8+ CTLs are activated by MHC class I molecules presenting endogenous or intracellular antigens, such as those produced from a viral infection or tumor cells.?

The majority of these cells have conventional TCRs formed by α and β peptide chains. However, a small percentage of T cells develop an unconventional TCR structure, consisting of γ and δ chains. This allows them to interact with a wide range of antigens – both endogenous and exogenous, self- and foreign antigens – in an MHC-independent manner. In contrast to αβ T cells, γδ T cells exhibit both innate and adaptive characteristics, allowing for early immune responses and surveillance at mucus membranes.

Written by Kate Harrison

Read the full article to learn about the specific T cell functions, conditions related to them and therapeutic applications.