Suppression of blastogenesis and proliferation of activated CD 4 + T cells: intravenous immunoglobulin ( IVI g) versus novel anti‐human leucocyte antigen ( HLA )‐ E monoclonal antibodies mimicking HLA ‐ I reactivity of IVIg

Summary Activated CD 4 + T cells undergo blastogenesis and proliferation and they express several surface receptors, including β2‐microglobulin‐free human leucocyte antigen ( HLA ) heavy chains (open conformers). Intravenous immunoglobulin (IVIg) suppresses activated T cells, but the mechanism is unclear. IVIg reacts with HLA ‐ I a/ I b antigens but its reactivity is lost when the anti‐ HLA ‐ E Ab is adsorbed out. Anti‐ HLA ‐ E antibodies may bind to the peptides shared by HLA ‐ E and the HLA ‐ I alleles. These shared peptides are cryptic in intact HLA , but exposed in open conformers. The hypothesis that anti‐ HLA ‐ E monoclonal antibodies ( mAb s) that mimic HLA ‐ I reactivity of IVIg may suppress activated T cells by binding to the shared peptides of the open conformers on the T cell surface was tested by examining the relative binding affinity of those mAb s for open conformers coated on regular beads and for intact HLA coated on iBeads, and by comparing the effects on the suppression of phytohaemagglutinin ( PHA )‐activated T cells of three entities: IVIg , anti‐ HLA ‐ E mAb s that mimic IVIg [Terasaki Foundation Laboratory (TFL)‐006 and (TFL )‐007]; and anti‐ HLA ‐ E antibodies that do not mimic IVIg ( TFL ‐033 and TFL ‐037). Suppression of blastogenesis and proliferation of those T cells by both IVIg and the anti‐ HLA ‐ E mAb s was dose‐dependent, the dose required with mAb s 50–150‐fold lower than with IVIg . TFL ‐006 and TFL ‐007 significantly suppressed blastogenesis and proliferation of activated CD 4 + T cells, but neither the non‐ IVIg ‐mimicking mAb s nor control antibodies did so. The suppression may be mediated by F ab‐binding of TFL ‐006/ TFL ‐007 to the exposed shared peptides. The mAb binding to the open conformer may signal T cell deactivation because the open conformers have an elongated cytoplasmic tail with phosphorylation sites (tryosine 320 /serine 335 ).