title: Anti-HLA-E monoclonal antibodies reacting with HLA-la and lb alleles like IVIg as potential IVIg-immunomimetics: an evolving therapeutic concept.
abstract: Healthy individuals have natural antibodies (Abs) reacting to allo-human leukocyte antigen (HLA)-la. 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-la after peptide inhibition assay. Sera or plasma of multiple donors are pooled to prepare intravenous immune globulin (IVIg). The HLA-la-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-la 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-la &-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.
authors.forename: Mepur H
authors.initials: MH
authors.lastname: Ravindranath
authors.forename: Dong
authors.initials: D
authors.lastname: Zhu
authors.forename: Tho
authors.initials: T
authors.lastname: Pham
authors.forename: Vadim
authors.initials: V
authors.lastname: Jucaud
authors.forename: Judy
authors.initials: J
authors.lastname: Hopfield
authors.forename: Satoru
authors.initials: S
authors.lastname: Kawakita
authors.forename: Paul I
authors.initials: PI
authors.lastname: Terasaki
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use*; D006680:HLA Antigens / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000276:immunology* / Q000627:therapeutic use; D014181:Transplantation Immunology / Q000276:immunology*; D000097625:HLA-E Antigens
chemical_list: D000911:Antibodies, Monoclonal; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D016756:Immunoglobulins, Intravenous; D000097625:HLA-E Antigens