論文

査読有り 国際誌
2019年11月26日

Evaluation of the Reactivity and Receptor Competition of HLA-G Isoforms toward Available Antibodies: Implications of Structural Characteristics of HLA-G Isoforms.

International journal of molecular sciences
  • Atsushi Furukawa
  • ,
  • Manami Meguro
  • ,
  • Rika Yamazaki
  • ,
  • Hiroshi Watanabe
  • ,
  • Ami Takahashi
  • ,
  • Kimiko Kuroki
  • ,
  • Katsumi Maenaka

20
23
記述言語
英語
掲載種別
DOI
10.3390/ijms20235947

The human leucocyte antigen (HLA)-G, which consists of seven splice variants, is a tolerogenic immune checkpoint molecule. It plays an important role in the protection of the fetus from the maternal immune response by binding to inhibitory receptors, including leukocyte Ig-like receptors (LILRs). Recent studies have also revealed that HLA-G is involved in the progression of cancer cells and the protection from autoimmune diseases. In contrast to its well characterized isoform, HLA-G1, the binding activities of other major HLA-G isoforms, such as HLA-G2, toward available anti-HLA-G antibodies are only partially understood. Here, we investigate the binding specificities of anti-HLA-G antibodies by using surface plasmon resonance. MEM-G9 and G233 showed strong affinities to HLA-G1, with a nM range for their dissociation constants, but did not show affinities to HLA-G2. The disulfide-linker HLA-G1 dimer further exhibited significant avidity effects. On the other hand, 4H84 and MEM-G1, which can be used for the Western blotting of HLA-G isoforms, can bind to native HLA-G2, while MEM-G9 and G233 cannot. These results reveal that HLA-G2 has a partially intrinsically disordered structure. Furthermore, MEM-G1, but not 4H84, competes with the LILRB2 binding of HLA-G2. These results provide novel insight into the functional characterization of HLA-G isoforms and their detection systems.

リンク情報
DOI
https://doi.org/10.3390/ijms20235947
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/31779209
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928721

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