An immunosuppressive and anti-inflammatory HLA class I-derived peptide binds vascular cell adhesion molecule-1

Background. A synthetic peptide corresponding to residues 75-84 of HLA-B270 2 modulates immune responses in rodents and humans both in vitro and in viv o. Methods, We used a yeast two-hybrid screening an in vitro biochemical metho d, and an in vivo animal model. Results. Two cellular receptors for this novel immunomodulatory peptide wer e identified using a yeast two-hybrid screen: immunoglobulin binding protei n (BiP), a member of the heat shock protein 70 family, and vascular cell ad hesion molecule (VCAM)-1, Identification of BiP as a ligand for this peptid e confirms earlier biochemical findings, while the interaction with VCAM-1 suggests an alternative mechanism of action. Binding to the B2702 peptide b ut not to closely related variants was confirmed by ligand Western blot ana lysis and correlated with immunomodulatory activity of each peptide. In mic e, an ovalbumin-induced allergic pulmonary response was blocked by in vivo administration of either the B2702 peptide or anti-VLA-4 antibody. Conclusions. We propose that the immunomodulatory effect of the B2702 pepti de is caused, in part, by binding to VCAM-1, which then prevents the normal interaction of VCAM-1 with VLA-4.