CoStimulatory Signals Are Required for Full TCell Activation

T-cell activation requires the dynamic interaction of multiple membrane molecules described above, but this interaction, by itself, is not sufficient to fully activate naive T cells. Naive T cells require more than one signal for activation and subsequent proliferation into effector cells:

■ Signal 1, the initial signal, is generated by interaction of an antigenic peptide with the TCR-CD3 complex.

■ A subsequent antigen-nonspecific co-stimulatory signal, signal 2, is provided primarily by interactions between CD28 on the T cell and members of the B7 family on the APC.

There are two related forms of B7, B7-1 and B7-2 (Figure 10-13). These molecules are members of the immunoglobu-lin superfamily and have a similar organization of extracellular domains but markedly different cytosolic domains. Both B7 molecules are constitutively expressed on dendritic cells and induced on activated macrophages and activated B cells. The ligands for B7 are CD28 and CTLA-4 (also known as CD152), both of which are expressed on the T-cell membrane as disulfide-linked homodimers; like B7, they are members of the immunoglobulin superfamily (Figure 10-13). Although CD28 and CTLA-4 are structurally similar glycoproteins, they act antagonistically. Signaling through

TCR-mediated signals

Cytoplasm

Ras-GDP (inactive)

Ras-GDP (active)

i Raf i MEK

MAP kinase

kinase pathway

Cytoplasm

^Elk HP

Nucleus

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Essentials of Human Physiology

Essentials of Human Physiology

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