Role of HLA-I Structural Variants and the Polyreactive Antibodies They Generate in Immune Homeostasis.

Autor: Ravindranath MH; Department of Hematology and Oncology, Children's Hospital, Los Angeles, CA 90027, USA.; Emeritus Research Scientist, Terasaki Foundation Laboratory, Santa Monica, CA 90064, USA., El Hilali F; Medico-Surgical, Biomedicine and Infectiology Research Laboratory, The Faculty of Medicine and Pharmacy of Laayoune & Agadir, Ibn Zohr University, Agadir 80000, Morocco., Amato-Menker CJ; Department of Microbiology, Immunology, and Cell Biology, School of Medicine, West Virginia University, Morgantown, WV 26506, USA., El Hilali H; Medico-Surgical, Biomedicine and Infectiology Research Laboratory, The Faculty of Medicine and Pharmacy of Laayoune & Agadir, Ibn Zohr University, Agadir 80000, Morocco., Selvan SR; Division of Immunology and Hematology Devices, OHT 7: Office of In Vitro Diagnostics, Office of Product Evaluation and Quality, Center for Devices and Radiological Health, Food and Drug Administration (FDA), Silver Spring, MD 20993, USA., Filippone EJ; Division of Nephrology, Department of Medicine, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19145, USA.
Jazyk: angličtina
Zdroj: Antibodies (Basel, Switzerland) [Antibodies (Basel)] 2022 Sep 08; Vol. 11 (3). Date of Electronic Publication: 2022 Sep 08.
DOI: 10.3390/antib11030058
Abstrakt: Cell-surface HLA-I molecules consisting of β2-microglobulin (β2m) associated heavy chains (HCs), referred to as Face-1, primarily present peptides to CD8+ T-cells. HCs consist of three α-domains, with selected amino acid sequences shared by all alleles of all six isoforms. The cell-surface HLA undergoes changes upon activation by pathological conditions with the expression of β2m-free HCs (Face-2) resulting in exposure of β2m-masked sequences shared by almost all alleles and the generation of HLA-polyreactive antibodies (Abs) against them. Face-2 may homodimerize or heterodimerize with the same (Face-3) or different alleles (Face-4) preventing exposure of shared epitopes. Non-allo immunized males naturally carry HLA-polyreactive Abs. The therapeutic intravenous immunoglobulin (IVIg) purified from plasma of thousands of donors contains HLA-polyreactive Abs, admixed with non-HLA Abs. Purified HLA-polyreactive monoclonal Abs (TFL-006/007) generated in mice after immunizing with Face-2 are documented to be immunoregulatory by suppressing or activating different human lymphocytes, much better than IVIg. Our objectives are (a) to elucidate the complexity of the HLA-I structural variants, and their Abs that bind to both shared and uncommon epitopes on different variants, and (b) to examine the roles of those Abs against HLA-variants in maintaining immune homeostasis. These may enable the development of personalized therapeutic strategies for various pathological conditions.
Competing Interests: The authors declare no conflict of interest.
Databáze: MEDLINE
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