CTLA-4 and T Cell Signaling

• Accessory surface proteins on lymphocytes are critical for activation.
• Regulatory features of lymphocyte surface proteins are connected to inhibitory mechanisms.
• These mechanisms greatly affect T cell proliferation and benefit the host.
• B7 ligand exists in two forms: B7-1 and B7-2.
• B7-1 and B7-2 bind to either CD28 or CTLA-4 on the T cell surface.
• Both B7 proteins are expressed as disulfide-linked homodimers.
• B7, CD28, and CTLA-4 are members of the immunoglobulin superfamily.
• CTLA-4's major structure and function are important in tumor immunology.

CTLA-4 and T Cell Signaling

• CD28 delivers a positive co-stimulatory signal to the T cell.
• CTLA-4 provides an inhibitory signal, downregulating activation.
• CTLA-4 is not detectable on resting T cells.
• CTLA-4 is detectable within 24 hours of stimulation of T cells.
• CTLA-4 levels increase proportionally to the stimulation of the CD28-generated co-stimulatory signal.

Regulatory Importance of CTLA-4

• CTLA-4 is also known as cytotoxic T lymphocyte-associated antigen 4.
• Attenuating T cell activation is important.
• Unregulated T cell proliferation leads to lipidopathy and spinomegaly.
• T cells possess a finite period of activity.
• If a T cell does not locate the appropriate antigen-MHC complex, it will be eliminated.
• If a T cell does not provide the appropriate signal to other immune cells (e.g., B cells) or transition to a memory T cell upon activation, it is down regulated.
• Upon activation, the cell surface protein CTLA-4 eventually binds B7.
• CTLA-4 binding to B7 results in energy or unresponsiveness.

T Cell Activation and Inhibition

• T cell activation and inhibition involve competition between CD28 and CTLA-4 (CD152) with B7 (CD80 or CD86).
• Inhibitory signals produced by engaging CTLA-4 are important to regulate specific humoral and cell-mediated immunity.

T Cell Activation and Regulation

• T cells are activated by antigen-presenting cells like macrophages.
• Macrophages express MHC class II, which binds peptides recognized by the T cell receptor.
• MHC class II and T cell receptor interaction gives a stimulatory signal for T cell activation.
• CD80 on the antigen-presenting cell and CD28 on the T cell surface provide co-stimulatory signals for T cell activation.
• T cell activation is necessary for activating B cells, which produce plasma cells and antibodies.
• T cell activation must be regulated to prevent hyperactivation and avoid worsening the situation.
• The T cell surface expresses CTLA-4 two days after activation.
• CTLA-4 is similar to CD28.
• CTLA-4 acts as an inhibitory signal, not a co-stimulatory signal.
• CD80 and CTLA-4 interact to give an inhibitory signal.
• CTLA-4 prevents CD28 from interacting with CD80.
• CTLA-4 sequesters ligands for the CD28 receptor, preventing T cell activation.
• The balance prevent total average abolition signal or the activated signal, but puts a great kind of thing.

CD28 vs. CTLA-4 in T Cell Regulation

CD28: Role in T Cell Activation

• CD28 provides a co-stimulatory signal to T cells by binding to CD80 (B7-1) and CD86 (B7-2) on antigen-presenting cells (APCs).
• Interacting with CD80/CD86 enhances T cell activation in the initial stages of immune responses.
• CD28 signaling promotes interleukin-2 (IL-2) production, supporting T cell proliferation and survival.
• CD28 engagement enhances T cell function, cytokine production, and development of effector responses against pathogens.
• CD28 engagement with CD80/CD86 provides a positive co-stimulatory signal.
• The positive co-stimulatory amplifies T cell activation and promote an effective immune response against pathogens.

CTLA-4: Role in T Cell Inhibition

• CTLA-4 competes with CD28 for binding to CD80/CD86 on APCs.
• CTLA-4 has a higher affinity for CD80/CD86 stronger than CD28, leading to the preferential binding of CTLA-4.
• CTLA-4 engagement delivers an inhibitory signal to T cells, suppressing their activation and function.
• CTLA-4 signaling downregulates IL-2 production, limiting the availability of this growth factor for T cell expansion.
• CTLA-4 plays a role in inducing peripheral tolerance by dampening excessive immune responses and preventing autoimmunity.
• CTLA-4 functions as an inhibitory checkpoint by inhibiting T cell activation and dampening immune responses in order to prevent excessive activation and autoimmunity.

Balancing Immune Responses

• CD28 provides a stimulatory signal, promoting T cell activation and immune responses against pathogens.
• CTLA-4 inhibits T cell activation, preventing excessive immune responses and contributing to immune tolerance.
• The balance between CD28 and CTLA-4 signaling is crucial for maintaining immune homeostasis
• Dyregulation of the balance can lead to autoimmune disorders or inadequate immune responses against infections.
• CD28 and CTLA-4 interact with CD80/CD86 on APCs, regulating T cell activation and inhibition