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Activation of T cells is initiated by engagement of cell-surface, antigen-specific T-cell receptors. However, additional signals delivered by CD28 family co-receptors, CD28, ICOS, CTLA-4 and PD-1, determine the type and extent of the immune response. Preclinical and phase I clinical studies have shown that manipulation of CD28 co-receptors and their ligands can enhance immunity against tumors. We have previously shown that PD-1 engagement negatively regulates CD4+ and CD8+ T cell responses. Importantly, PD-L1, the ligand for PD-1, is expressed on a variety of human carcinomas and melanomas. My interest is to understand the role of PD-1 in T cell activation using viral and tumor antigen-specific T cell models. These studies will provide insight into the potential targeting of the PD-1 pathway for improved cell-based therapies against melanoma.

Proposed periodic arrangement of CTLA-4 molecules on the surface of a T cell bound to B7-1 molecules on the surface of an antigen-presenting cell. This model is based on the molecular association of CTLA-4 and B7.1 observed in the crystal lattice structure. The proposed lattice structure would enhance the stability of CTLA-4 and B7.1 interactions on the cell surface.
From: Collins M, Ling V, Carreno BM, The B7 family of immune-regulatory ligands. Genome Biol 2005;6(6):223

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Updated: June 4, 2008