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expert reviews

in molecular medicine

APC

T cell

Antigen taken up in APC and partially digested

CD86

CTLA-4 b

Fyn Lck

Inhibitory signal MHC TCR CD3 c CTLA-4 ITAM Peptide Stimulatory signal

ZAP-70

CD80

CD28

Proposed mechanisms by which CTLA-4 inhibits T-cell activation

Expert Reviews in Molecular Medicine C 2005 Cambridge University Press

Figure 2. Proposed mechanisms by which CTLA-4 inhibits T-cell activation. (a) CTLA-4 might successfully compete with CD28 for CD80/86 ligands and thereby inhibit the costimulatory effect of CD28. (b) CTLA-4 might interact with Lck, Fyn and ZAP-70 through SHP1 phosphatase to prevent constitutive expression of downstream signalling pathways. (c) CTLA-4 might directly interact with the TCRCD3 complex at the immunological synapse to disrupt T-cell activation by binding and blocking the immunoreceptor tyrosine-based activation motif (ITAM). Abbreviations: APC, antigen-presenting cell; CTLA-4, cytotoxic T-cell-associated 4; MHC, major histocompatibility complex; TCR, T-cell receptor.

Accession information: Vol. 7; Issue 23; 18 October 2005 2005 Cambridge University Press

Proposed mechanisms by which CTLA-4 inhibits T-cell activation