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.
Xingxing Zang, James P. Allison
Phylogeny of VSIG4 and hypothetical models of its role as a T cell inhibitor.