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T Cell Activation
MHC, Co-stimulation, and Effector Subtypes
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T cell activation is a central event in adaptive immunity because it determines whether the body mounts a targeted immune response against infection, cancer, or abnormal cells. A naive T cell does not respond to antigen alone. It must receive a coordinated set of signals from an antigen presenting cell at the immunologic synapse. Understanding these signals helps explain normal immune defense, vaccine responses, transplant rejection, and many immunotherapies.
The first activation signal is antigen recognition, where the T cell receptor binds a peptide presented by major histocompatibility complex molecules on the APC. The second signal is co stimulation, most importantly CD28 on the T cell binding B7 molecules on the APC, which prevents anergy and supports survival and proliferation. Cytokines then provide a third signal that directs differentiation into effector subtypes such as Th1, Th2, Th17, Tfh, Treg, or cytotoxic CD8 T cells. Each subtype produces distinct cytokines and carries out specialized immune functions in tissues.
Key Facts
- Signal 1: TCR + CD3 binds peptide MHC on the APC.
- MHC I presents endogenous peptides to CD8 T cells; MHC II presents exogenous peptides to CD4 T cells.
- Signal 2: CD28 on T cells binds B7-1 (CD80) or B7-2 (CD86) on APCs.
- Without co stimulation, antigen recognition can lead to anergy or functional unresponsiveness.
- IL-2 promotes clonal expansion of activated T cells through autocrine signaling.
- CTLA-4 and PD-1 are inhibitory receptors that reduce T cell activation and help maintain peripheral tolerance.
Vocabulary
- Immunologic synapse
- The organized contact region between a T cell and an antigen presenting cell where signaling molecules cluster during activation.
- Major histocompatibility complex (MHC)
- A set of cell surface proteins that display peptide antigens for recognition by T cells.
- Co stimulation
- A second activating signal, such as CD28 binding B7, that is required along with antigen recognition for full T cell activation.
- Anergy
- A state in which a lymphocyte remains alive but becomes unresponsive to antigen stimulation.
- Effector T cell subtype
- A differentiated T cell population with a specific cytokine pattern and immune function, such as Th1, Th2, Th17, Tfh, Treg, or cytotoxic T cells.
Common Mistakes to Avoid
- Assuming antigen binding alone activates a naive T cell, which is wrong because full activation usually requires both peptide MHC recognition and co stimulation.
- Confusing MHC I with MHC II, which is wrong because MHC I mainly activates CD8 T cells while MHC II mainly activates CD4 T cells.
- Thinking all activated CD4 T cells become the same helper cell type, which is wrong because local cytokines drive different effector fates with different functions.
- Forgetting inhibitory checkpoints such as CTLA-4 and PD-1, which is wrong because activation is balanced by negative regulators that limit tissue damage and autoimmunity.
Practice Questions
- 1 An APC presents a viral peptide on MHC I to a naive T cell and also expresses B7. Which T cell coreceptor is expected on the responding T cell, and what is the main effector function of the activated cell?
- 2 A naive T cell recognizes peptide MHC on an APC but receives no CD28 to B7 co stimulation. What functional outcome is most likely, and why?
- 3 A patient has an infection with an intracellular bacterium. Explain why a Th1 biased response would be more useful than a Th2 biased response in this situation.