Anti-HLA-E Monoclonal Antibodies Reacting with HLA-1a and 1b Alleles Like IVIg as Potential IVIg-Immunomimetics: An Evolving Therapeutic Concept.

Ravindranath MH, Zhu D, Pham T, Jucaud V, Hopfield J, Kawakita S, Terasaki PI.

Clinical Transplants 2013, Chapter 35

Abstract

Healthy individuals have natural antibodies (Abs) reacting to allo-human leukocyte antigen (HLA)-1a. This could be due to the presence of anti-HLA-E immunoglobulin G (IgG), which was revealed to recognize the peptides shared between HLA-E and HLA-1a after peptide inhibition assay. Sera or plasma of multiple donors are pooled to prepare intravenous immune globulin (IVIg). The HLA-1a-reactivity of IVIg is abolished when the anti-HLA-E Abs are depleted from the IVIg, suggesting that IVIg contains anti-HLA-E Abs with HLA-1a reactivity. Anti-HLA-E monoclonal antibodies (mAbs; e.g., TFL-006 and TFL-007) generated at Terasaki Foundation Laboratory (TFL) differ from commercial HLA-E mAbs in mimicking HLA-1a &-lb reactivities of IVIg, which is known to suppress the allo-HLA antibody (Ab) production and the activated CD4 T cells. Whether HLA-E-mAbs also have the ability to suppress the production of these Abs and activation of T cells like IVIg is evaluated. Indeed, the TFL-mAbs significantly suppressed the allo-HLA-ll Ab production by B cells obtained from a woman alloimmunized postpartum >20 years ago. Similarly, the TFL-mAbs suppressed HLA-I Ab produced by a B-cell hybridoma. In both instances, the suppression was far superior to that by IVIg. Activated T cells were suppressed by both IVIg and the TFL-mAbs dosimetrically. Furthermore, the required concentrations of TFL-mAbs are 150-fold lower than the concentrations of IVIg required for the suppression.