The γ-IFN-inducible lysosomal thiol reductase (GILT) is a unique thiol reductase with optimal activity at low pH, and is expressed in Ag presenting cells (APC). GILT is critical to processing protein Ag by catalyzing disulfide bond reduction, thus facilitating the unfolding of native Ag containing disulfide bonds for further processing. GILT-/- mice are defective in processing exogenous protein Ag. However the role of GILT in Ab response is not clear. Here we report that after immunization, GILT-/- mice failed to produce Ab to exogenous bovine insulin (bIns), which has A and B chains and contains both inter and intra-chain disulfide bonds, while Ab response to OVA was normal in both GILT-/- and wt B6 mice. GILT-/- APC was able to present bIns to an insulin B chain peptide-specific T hybridoma, although it produced less amounts of IL2, compared to when using B6 APC. IL2 production was MHC-II mediated (could be blocked by α-mouse, but not α-human, MHC-II Ab) and the reduced IL2 production of GILT-/- cells was bIns-specific since GILT-/- APC could not present HEL, another Ag containing disulfide bonds, to an HEL-specific T hybridoma to produce IL2. This data indicates that the T cell response to bIns is only partially affected in GILT-/- mice, which was further supported by the fact that CFSE labeled, in vivo bIns primed, GILT-/- CD4 cells proliferated equally well as wt B6 CD4 cells upon restimulation by bIns. Our data indicates a novel role of GILT in Ab response to insulin.
- Copyright © 2011 by The American Association of Immunologists, Inc.