Cutting Edge: Class II-like Structural Features and Strong Receptor Binding of the Nonclassical HLA-G2 Isoform Homodimer.
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Kuroki K, Mio K, Takahashi A, Matsubara H, Kasai Y, Manaka S, Kikkawa M, Hamada D, Sato C, Maenaka K
Cutting Edge: Class II-like Structural Features and Strong Receptor Binding of the Nonclassical HLA-G2 Isoform Homodimer.
J Immunol. 2017 May 1;198(9):3399-3403. doi: 10.4049/jimmunol.1601296. Epub 2017 Mar 27.
- PubMed ID
- 28348268 [ View in PubMed]
- Abstract
HLA-G is a natural tolerogenic molecule and has the following unique features: seven isoforms (HLA-G1 to HLA-G7), formation of disulfide-linked homodimers, and beta2-microglobulin (beta2m)-free forms. Interestingly, individuals null for the major isoform, HLA-G1, are healthy and expressed the alpha2 domain-deleted isoform, HLA-G2, which presumably compensates for HLA-G1 function. However, the molecular characteristics of HLA-G2 are largely unknown. In this study, we unexpectedly found that HLA-G2 naturally forms a beta2m-free and nondisulfide-linked homodimer, which is in contrast to the disulfide-bonded beta2m-associated HLA-G1 homodimer. Furthermore, single-particle analysis, using electron microscopy, revealed that the overall structure and domain organization of the HLA-G2 homodimer resemble those of the HLA class II heterodimer. The HLA-G2 homodimer binds to leukocyte Ig-like receptor B2 with slow dissociation and a significant avidity effect. These findings provide novel insights into leukocyte Ig-like receptor B2-mediated immune regulation by the HLA-G2 isoform, as well as the gene evolution of HLA classes.