Human leukocyte antigen G (HLA-G), a non classical class HLA I antigen, is an important immune regulator in homeostasis and disease progression. Biological and clinical significance of HLA-G expression and genetic variation of HLA-G in different setting have been extensively investigated since its discovery.In this Research Topic "The Biological and Clinical Aspects of HLA-G volume II", fifteen in-depth reviews, perspectives and original research articles on different aspects of HLA-G were published, which focused on HLA-G/receptors in cancer, autoimmune and infectious diseases, skin, allergy and reproduction immunity.Multiple HLA-G isoforms generated by primary transcript alternative splicing were identified, such as 1 domain-containing (HLA-G1~HLA-G7) and 1 domain-deleted isoforms. Given to each isoform with distinct molecule structure or specific allelic product with distinct amino acid substitution, biological function of those structural diverse HLA-G molecules can be expected. HLA-G/receptor signaling has been observed to benefit fetal-maternal immune tolerance, limit inflammation, and prolong transplanted grafts acceptance, while impair host immune responses against virally infected cells and malignant cells and enhance the capability of these abnormal cells to escape immune clearance. Receptors immunoglobulin-like transcripts 2/ILT2, ILT4, KIR2DL4 have been recognized to interact 1 domain-containing HLA-G isoforms with immunosuppressive functions. In this regard, an increasing number of clinical trials on HLA-G and/or ILTs targeted immunotherapy for solid cancers have been lanuched. However, 1 domain-deleted isoform has been recently found to be with stimulatory property, implying complexicity of HLA-G molecule which requires to be explored. HLA-G/receptor-targeted immunotherapy. We deeply appreciate all contributions from authors, reviewers and editors alike.
W-HY and JL wrote the manuscript.
