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Review

Therapeutic Potential of HLA-I Polyreactive mAbs Mimicking the HLA-I Polyreactivity and Immunoregulatory Functions of IVIg

1
Department of Hematology and Oncology, Children’s Hospital, Los Angeles, CA 90027, USA
2
Emeritus Research Scientist at Terasaki Foundation Laboratory, Santa Monica, CA 90064, USA
3
Mohamed V. Hospital, Mekines 50060, Morocco
4
Division of Nephrology, Department of Medicine, Sidney Kimmel Medical College at Thomas Jefferson Univsity, Philadelphia, PA 19145, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Tatsuya Yamazaki
Vaccines 2021, 9(6), 680; https://doi.org/10.3390/vaccines9060680
Received: 28 April 2021 / Revised: 3 June 2021 / Accepted: 5 June 2021 / Published: 21 June 2021
(This article belongs to the Special Issue Research on Monoclonal Antibodies and Antibody Engineering)
HLA class-I (HLA-I) polyreactive monoclonal antibodies (mAbs) reacting to all HLA-I alleles were developed by immunizing mice with HLA-E monomeric, α-heavy chain (αHC) open conformers (OCs). Two mAbs (TFL-006 and TFL-007) were bound to the αHC’s coated on a solid matrix. The binding was inhibited by the peptide 117AYDGKDY123, present in all alleles of the six HLA-I isoforms but masked by β2-microglobulin (β2-m) in intact HLA-I trimers (closed conformers, CCs). IVIg preparations administered to lower anti-HLA Abs in pre-and post-transplant patients have also shown HLA-I polyreactivity. We hypothesized that the mAbs that mimic IVIg HLA-I polyreactivity might also possess the immunomodulatory capabilities of IVIg. We tested the relative binding affinities of the mAbs and IVIg for both OCs and CCs and compared their effects on (a) the phytohemagglutinin (PHA)-activation T-cells; (b) the production of anti-HLA-II antibody (Ab) by B-memory cells and anti-HLA-I Ab by immortalized B-cells; and (c) the upregulation of CD4+, CD25+, and Fox P3+ T-regs. The mAbs bound only to OC, whereas IVIg bound to both CC and OC. The mAbs suppressed blastogenesis and proliferation of PHA-activated T-cells and anti-HLA Ab production by B-cells and expanded T-regs better than IVIg. We conclude that a humanized version of the TFL-mAbs could be an ideal, therapeutic IVIg-mimetic. View Full-Text
Keywords: intravenous immunoglobulin (IVIg); human leukocyte antigen-I (HLA-1); polyreactive mAbs; monospecific mAbs; shared epitopes; immunosuppression; T-cells; B-memory cells; T-regulatory cells; blastogenesis; proliferation; antibody production intravenous immunoglobulin (IVIg); human leukocyte antigen-I (HLA-1); polyreactive mAbs; monospecific mAbs; shared epitopes; immunosuppression; T-cells; B-memory cells; T-regulatory cells; blastogenesis; proliferation; antibody production
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MDPI and ACS Style

Ravindranath, M.H.; Hilali, F.E.; Filippone, E.J. Therapeutic Potential of HLA-I Polyreactive mAbs Mimicking the HLA-I Polyreactivity and Immunoregulatory Functions of IVIg. Vaccines 2021, 9, 680. https://doi.org/10.3390/vaccines9060680

AMA Style

Ravindranath MH, Hilali FE, Filippone EJ. Therapeutic Potential of HLA-I Polyreactive mAbs Mimicking the HLA-I Polyreactivity and Immunoregulatory Functions of IVIg. Vaccines. 2021; 9(6):680. https://doi.org/10.3390/vaccines9060680

Chicago/Turabian Style

Ravindranath, Mepur H., Fatiha E. Hilali, and Edward J. Filippone 2021. "Therapeutic Potential of HLA-I Polyreactive mAbs Mimicking the HLA-I Polyreactivity and Immunoregulatory Functions of IVIg" Vaccines 9, no. 6: 680. https://doi.org/10.3390/vaccines9060680

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