T cells, a type of white blood cell, are an important part of the body’s immune system. These cells are known for their “antigen specificity,” meaning each T cell is uniquely programmed to identify and respond to a particular foreign substance, or antigen. This specialization allows the immune system to target specific threats with precision, initiating a tailored response against invaders like viruses, bacteria, or abnormal cells.
How T Cells Acquire Specificity
T cells originate from hematopoietic stem cells in the bone marrow and then travel to the thymus, a specialized organ where they mature and gain specificity. Within the thymus, each developing T cell, or thymocyte, undergoes a genetic rearrangement process to create a distinct T-cell receptor (TCR). This TCR acts like a lock, designed to recognize a single, specific antigenic “key.”
This genetic rearrangement of the TCR alpha and beta chains occurs at different stages of T-cell development within the thymus. After forming a candidate TCR, thymocytes undergo “thymic education” involving two selection processes: positive and negative selection. Positive selection ensures that T cells can recognize the body’s own Major Histocompatibility Complex (MHC) molecules, which are essential for antigen presentation. Negative selection eliminates T cells that react too strongly to self-antigens, preventing the immune system from attacking healthy body tissues.
How T Cells Recognize Antigens
Mature T cells identify targets through interaction with other cells. T cells do not directly detect whole pathogens; instead, they recognize small fragments (antigens) displayed on the surface of other cells. This display occurs on Major Histocompatibility Complex (MHC) molecules.
Two main classes of MHC molecules are involved: MHC Class I and MHC Class II. MHC Class I molecules are found on nearly all nucleated cells and typically present antigens derived from proteins produced inside the cell, such as those from viral infections or cancerous transformations. MHC Class II molecules are primarily expressed on specialized cells called antigen-presenting cells (APCs), including dendritic cells, macrophages, and B cells.
APCs process and present antigens derived from extracellular sources, like bacteria, onto their MHC Class II molecules. The T-cell receptor then binds to this antigen-MHC complex. This recognition, along with co-stimulatory signals from the APC, leads to T cell activation.
Diverse Functions of Specific T Cells
Once activated, T cells differentiate into various subtypes, each with a specialized role. Helper T cells, also known as CD4+ T cells, serve as orchestrators of the immune system. Upon activation, they release cytokines, which activate other immune cells, including B cells for antibody production, cytotoxic T cells, and macrophages.
Cytotoxic T cells, or CD8+ T cells, recognize and destroy infected body cells or cancer cells that display specific antigens on MHC Class I molecules. This elimination process prevents the spread of infection and removes abnormal cells. Regulatory T cells, or Tregs, play a balancing role in the immune system. They help to suppress excessive immune responses and prevent autoimmunity.
Antigen-Specific T Cells in Health and Disease
Antigen-specific T cells are essential for health and protection against various threats. They are crucial for defending the body against infections, including viral and bacterial pathogens, by directly eliminating infected cells or coordinating broader immune responses. These cells also contribute to cancer surveillance, identifying and destroying transformed cells before they can develop into tumors. Their specificity is harnessed in modern cancer immunotherapies, such as CAR T-cell therapy, where T cells are engineered to target specific tumor antigens.
However, T cell specificity can sometimes be misdirected. In autoimmune diseases, T cells erroneously target and attack healthy tissues, leading to chronic inflammation and tissue damage. The development of “memory” T cells is also key to vaccine effectiveness. After an initial encounter with an antigen (through infection or vaccination), a subset of T cells survives as long-lived memory cells, providing rapid protection upon subsequent exposure.