Cell Adhesion Molecules Facilitate TCRMediated Interactions

CD2 and the integrin LFA-1 are cell-adhesion molecules on the surfaces of T cells that bind, respectively, to LFA-3 and ICAMs (intracellular cell-adhesion molecules) on antigen-presenting cells and various target cells (see Figure 9-13). The level of LFA-1 and CD2 is twofold to fourfold higher on effector T cells than on naive T cells, enabling the effector T cells to bind more effectively to antigen-presenting cells and to various target cells that express low levels of ICAMs or LFA-3.

As Chapter 9 showed, the initial interaction of an effector T cell with an antigen-presenting cell or target cell is weak, allowing the TCR to scan the membrane for specific peptides

Comparison of naive and effector T cells

Property

Naive T cells

Effector T cells

Co-stimulatory signal (CD28-B7 interaction) CD45 isoform

Cell-adhesion molecules (CD2 and LFA-1) Trafficking patterns

Required for activation

CD45RA

HEVs* in secondary lymphoid tissue

Not required for activation

CD45RO

High

Tertiary lymphoid tissues; inflammatory sites

*HEV = high endothelial venules, sites in blood vessel used by lymphocytes for extravasation.

Effector molecules produced by effector T cells

Cell type

Soluble effectors

Membrane-bound effectors

CTL Th1

Cytotoxins (perforins and granzymes), IFN-7, TNF-p IL-2, IL-3, TNF-p, IFN-7, GM-CSF (high) IL-3, IL-4, IL-5, IL-6, IL-10, IL-13, GM-CSF (low)

Fas ligand (FASL)

CD40 ligand presented by self-MHC molecules. If no peptide-MHC complex is recognized by the effector cell, it will disengage from the APC or target cell. Recognition of a peptide-MHC complex by the TCR, however, produces a signal that increases the affinity of LFA-1 for ICAMs on the APC or target-cell membrane, prolonging the interaction between the cells. For example, TH1 effector cells remain bound to macrophages that display peptide-class II MHC complexes; TH2 effector cells remain bound to B cells that display peptide-class II MHC complexes; and CTL effector cells bind tightly to virus-infected target cells that display peptide-class I MHC complexes.

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