[HLA-G: an immunoregulatory non classical class I HLA molecule]

Area of Science:

• Immunology
• Molecular Biology
• Genetics

Context:

• Human Leukocyte Antigen-G (HLA-G) is a non-classical HLA class I molecule with restricted tissue expression and low polymorphism.
• Despite its limited variation, HLA-G significantly influences innate and adaptive immunity.

Purpose:

• This review elucidates the immunomodulatory functions of HLA-G.
• It explores the association between HLA-G and various pathological conditions, including pregnancy complications, cancer progression, and transplant rejection.
• The review also highlights recent discoveries concerning novel functional homomultimeric isoforms of HLA-G.

Summary:

• HLA-G exhibits tolerogenic properties, crucial for immune tolerance during early conception by protecting fetal tissues from maternal immune attack.
• Aberrant levels of soluble HLA-G or specific allelic expressions are linked to pregnancy complications.
• In cancer, HLA-G expression on tumor cells facilitates immune evasion through mechanisms like trogocytosis and regulatory T cell induction, correlating with invasiveness and clinical outcomes.
• Furthermore, HLA-G plays a role in protecting transplanted tissues from rejection.

Impact:

• Understanding HLA-G's multifaceted roles provides critical insights into immune regulation in reproduction, oncology, and transplantation.
• The identification of new HLA-G isoforms opens avenues for improved diagnostics and therapeutic strategies targeting immune-related diseases.
• This knowledge can advance treatments for pregnancy complications, enhance cancer immunotherapy, and improve transplant success rates.