Suppression of blastogenesis and proliferation of activated CD4+ T cells: intravenous immunoglobulin (IVIg)versusnovel anti-human leucocyte antigen (HLA)-E monoclonal antibodies mimicking HLA-I reactivity of IVIg

Abstract

Summary Activated CD4+ T cells undergo blastogenesis and proliferation and they express several surface receptors, including β2-microglobulin-free human leucocyte antigen (

Immunoglobulin (Ig)G purified from human sera mirrors intravenous Ig human leucocyte antigen (HLA) reactivity and recognizes one's own HLA types, but may be masked by Fab complementarity-determining region peptide in the native sera

“…Besides the questionable immunosuppressive effect of IVIg [34,35], as used routinely in transplant patients, there is the imminent danger of HLA-reactive IVIg preparations producing transfusion-related acute lung injury (TRALI). Variations in the IVIg preparation can make it more toxic.…”

“…It appears that the IgG may react to intact HLA-A alleles and to the open conformers of HLA-B and HLA-Cw. However, in some individuals the reactivity may reverse, as noted: anti-HLA-I IgG to intact HLA may produce TRALI, whereas antibodies against open conformers may effect immunosuppression [34,35].…”

Immunobiology of HLA Class-Ib Molecules in Transplantation

“…HLA-G is capable of modulating the adaptive immunity [20], as well as exerting antigen-presenting functions, although the latter is not its primary function [21,22]. HLA-Ib molecules also can generate a pool of antibodies in vivo, which can be either monospecific or polyreactive (cross-reactive with other HLA-I molecules) [23,24], thus pointing out the immunogenic potential of HLA-Ib molecules in vivo [25][26][27]. The specificity of such antibodies can impact the outcome of transplantation, as well as the allocation of organs.…”

“…Routinely, only HLA-Ia and -II antibodies are tested in transplant recipients, and HLA-Ib antibodies are never considered. However, various investigations [23,24,39,[104][105][106][107] of HLA-Ib antibodies showed that one molecule of HLA-Ib (with or without β2m) can elicit different kinds of mAbs, some recognizing strictly the HLA immunogen used in immunization. Alternatively, these antibodies (e.g., HLA-E mAb TFL-033) [23,39] can be considered monospecific since they react to only one HLA-Ib molecule.…”

Immunobiology of Allograft Human Leukocyte Antigens in the New Microenvironment

“…This in turn signaled T-cell deactivation leading to suppression of blastogenesis and proliferation. A signal-transducing function of the cytoplasmic tail is implicated because, in contrast to β2m-associated HC, β2m-free HLA molecules, overexpressed on activated T lymphocytes, have an elongated cytoplasmic tail (the consequence of exon 6 and 7) with phosphorylation sites (tyrosine and serine at, respectively, positions 320 and 335) [94][95][96].…”