HLA-G*0105N null allele encodes functional HLA-G isoforms.

Magali Le Discorde (1) , Caroline Le Danff (1) , Philippe Moreau (2) , Nathalie Rouas-Freiss (2) , Edgardo D Carosella (2)

1 DSV/DRM
2 SRHI - UMR_E 05 - Service de Recherche en Hémato-Immunologie

Expression of the nonclassical HLA class I antigen, HLA-G, is associated with immune tolerance in view of its role in maintaining the fetus in utero, allowing tumor escape, and favoring graft acceptance. Expressed on invasive trophoblast cells, HLA-G molecules bind inhibitory receptors on maternal T lymphocytes and NK cells, thereby blocking their cytolytic activities and protecting the fetus from maternal immune system attack. The HLA-G gene consists of 15 alleles, including a null allele, HLA-G*0105N. HLA-G*0105N presents a single base deletion, preventing translation of both membrane-bound (HLA-G1) and full-length soluble isoforms (HLA-G5) as well as of the spliced HLA-G4 isoform. The identification of healthy subjects homozygous for this HLA-G null allele suggests that the HLA-G*0105N allele may generate other HLA-G isoforms, such as membrane-bound HLA-G2 and -G3 and the soluble HLA-G6 and -G7 proteins, which may substitute for HLA-G1 and -G5, thus assuming the immune tolerogeneic function of HLA-G. To investigate this point, we cloned genomic HLA-G*0105N DNA and transfected it into an HLA-class I-positive human cell line. The results obtained indicated that HLA-G proteins were indeed present in HLA-G*0105N-transfected cells and were able to protect against NK cell lysis. These findings emphasize the role of the other HLA-G isoforms as immune tolerogeneic molecules that may also contribute to maternal tolerance of the semiallogenic fetus as well as tumor escape and other types of allogeneic tissue acceptance.

Domains: Life Sciences [q-bio]; Immunology

Magali Le Discorde, Caroline Le Danff, Philippe Moreau, Nathalie Rouas-Freiss, Edgardo D Carosella. HLA-G*0105N null allele encodes functional HLA-G isoforms.. Biology of Reproduction, 2005, 73 (2), pp.280-8. ⟨10.1095/biolreprod.104.037986⟩. ⟨cea-00268875⟩