Cell Surface B2m-Free Human Leukocyte Antigen Monomers and Dimers: Are They Neo-HLA Class and Proto-HLA?

The review explores the existence and significance of B2m-free Human Leukocyte Antigen (HLA) heavy chain (HC) variants, termed Face-2, Face-3, and Face-4, which can form monomers and dimers distinct from traditional HLA trimers. These B2m-free HCs are upregulated in immune cells upon activation and are involved in various immune functions and disease processes, including spontaneous arthritis in HLA-B27+ mice and certain human cancers. The study suggests these variants might represent a new class of HLA, potentially termed neo-HLA, due to their unique structural and functional properties. The research highlights the importance of understanding these dimers in personalized immunotherapy, transplant rejection, and disease pathology, and suggests further investigation into their roles in normal and malignant cells.