Interaction between T-cell and antigen-presenting cell
cell cell interaction
stepS:
.A. Molecules Involved in Interactions between T Cells and APCs
Several adhesion and accessory molecules promote the interaction of T cells with antigen presenting cells (APCs), such as B cells. dendritic cells (DES). and monocytes.
Leukocyte function associated antigen 1 [LFA 1). a ubiquitous antigen, binds to intercellular adhesion molecule 1 (ICAM 1). CD2 binds to LFA 3. a glycoprotein. which is mainly ex pressed on endothelial cells, epithelial cells, and connective tissue.
The CD40/CD40 ligand interaction transmits a survival signal to germinal center B cells and induces DCs to mature and produce large quantities of IL 12.
The adhesion of B cells to T cells is further stabilized by interactions of the CD106 antigen. or vascular cell adhesion molecule 1 (VCAM 1), which is also expressed on endothelial cells. with the CD49d antigen, also called very late antigen 4 (VLA-4) on activated T cells.
The interaction of the T cell molecule CD28 with CDSO/CDSB on APCs has a stimulatory effect, whereas the interaction of CD152. or cytotoxic T lympho cytes antigen 4 (CTLA 4), with the same anti gens has an inhibitory effect;
B. Several Signals Are Needed for T-Cell Activation
Antigen recognition by the T cell receptor (TCR) provides a First activating signal for a T cell, but it is not sufficient to induce full activation. In the absence of a second signal, the T cell becomes tolerant or anergic.
The second signal is provided by the interaction of the CD28 antigen. which is constitutionally expressed on resting T cells. with the co stimulatory molecules 37.1 (CD80) or B72 {CD86) on APCS. 0n activation by both signals. the antigen CTLA-4 (CD152) is upregulated in T cells within 24-48 hours. CTLA 4 is a higher affinity receptor for CDSO/ CD86: it competes with CD28 and inhibits cell cycle progression.
This negative signal is prob ably emitted by CTLA 4 to end T cell activation in order to prevent an exaggerated immune response.
A further inhibitory receptor is known as programmed death gene 1 (PD 1). which can interact with two B7 family members: PD L1 or B7 Hi and PD L2 or B7 DC
Terminally differentiated DCs can produce large quantities of IL 12 on CD40/CD40 ligand interaction, inducing the release of interferon y (IFN 7) and the differentiation of CD4+ cells into TH1 cells. IL 12 is also a direct and potent stimulus of cytotoxic T lymphocytes (CTLs) and natural killer cell (NK) function. IFN y stimulates antimicrobial and pro inflammatory activity of macrophages and enhances the activation of CTLs.
C. ICOS in T Cell Activation
Unlike C028. the CD28 homologous inducible T cell co stimulator (ICOS) is not constitutively expressed on resting T cells but only after activation via TCR/CD3 complex.
Engagement of ICOS. like CD28. can mediate potent co stimu lation of Tcells and promote proliferation. Re cent studies indicate that stimulation via ICOS can induce both TH] and TH2 differentiation. ICOS interacts with the ICOS ligand ICOSL,
which is also known as B7h. B7RP 1. and 87 H2. ICOSL is expressed constitutively on B cells, DCs. macrophages. and endothelial cells. and it is upregulated by TNF u or inflammatory stimuli.
D. Superantigen Stimulation
Superantigens are mainly bacterial products (e.g.. staphylococcal enterotoxins) or viral proteins that induce nonselective T cell activation.
The response of T cells to superantigens is not clonal; a large number of different T cells are activated. While a highly specific interaction of the processed peptide embedded in the MHC complex with the a and B chain of the TCR is mandatory during antigen specific T cell activation.
superantigens do not require intracellular processing. They bind as whole proteins to the outer side of the VB region of several TCRs. Around 100 times more T cells react with superantigens than with normal antigens. Some superantigens induce activation of up to 10 % of peripheral blood T cells. On superantigen activation. CD4+ T cells release a high amount of cytokines. which can mediate toxic effects in the host.
Post a Comment