To be or not to be B7
Xingxing Zang, James P. Allison
Xingxing Zang, James P. Allison
Published October 2, 2006
Citation Information: J Clin Invest. 2006;116(10):2590-2593. https://doi.org/10.1172/JCI30103.
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Commentary

To be or not to be B7

Abstract

The activation of lymphocytes and development of adaptive immune responses is initiated by the engagement of TCRs by antigenic peptide–MHC complexes and shaped at the clonal level by both positive and negative costimulatory signals. The B7 family members are involved at several stages in this process. In this issue of the JCI, Vogt et al. show that the B7 family–related protein V-set and Ig domain–containing 4 (VSIG4) can act as an inhibitor of T cell activation (see the related article beginning on page 2817). Intriguingly, the same molecule was recently independently identified as a complement receptor of the Ig superfamily (CRIg) and was convincingly demonstrated to be a receptor for complement component 3 fragments. These findings raise interesting questions regarding the physiological roles and mechanisms of action of this molecule. Identification of dual functions of this molecule provides an additional level of complexity in T cell costimulation.

Authors

Xingxing Zang, James P. Allison

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Figure 1

Phylogeny of VSIG4 and hypothetical models of its role as a T cell inhibitor.

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Phylogeny of VSIG4 and hypothetical models of its role as a T cell inhib...
(A) VSIG4, A33, and junctional adhesion molecule A (JAM-A) are grouped together in a phylogenetic tree, whereas representatives of the B7 family (B7-1, CD274, and V-set domain–containing T cell activation inhibitor 1 [VTCN1]) and CR1 and CR2 are divergent. All the sequence alignments and homology comparisons were performed with MacVector 7.0. (Accelrys). The phylogenetic tree was generated by Phylogenetic Analysis Using Parsimony (PAUP 4.0b10; Sinauer Associates Inc.) with sequence alignment by removal of significant inserts and trimming C- and N-terminal extensions. (B) T cells express an unidentified receptor for VSIG4 expressed on macrophages. The ligation of this receptor downregulates TCR-mediated signaling to the nucleus. Alternatively, VSIG4 on macrophages and CR1/CR3 on T cells bind the same multimeric C3b or iC3b molecules, which in turn triggers a signal resulting in inhibition of T cell activation.