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

Cell surface HLA-I molecules (Face-1) consist of a polypeptide heavy chain (HC) with two groove domains (G domain) and one constant domain (C-domain) as well light chain, B2-microglobulin (B2m). However, HCs can also independently emerge unfolded on the cell without peptides B2m-free HC monomers (Face-2), homodimers (Face 3), heterodimers (Face-4). The transport these HLA variants from ER to was confirmed by antiviral antibiotics that arrest release newly synthesized proteins ER. Face-2 occurs at low levels normal lung, bronchi, epidermis, esophagus, breast, stomach, ilium, colorectum, gall bladder, urinary seminal vesicles ovarian epithelia, endometrium, thymus, spleen, lymphocytes. They are upregulated immune cells upon activation proinflammatory cytokines, anti-CD3 antibodies, (e.g., ionomycin), phytohemagglutinin, retinoic acid, phorbol myristate acetate. Their density remains high long remain in an activated state. After activation-induced upregulation, undergo homo- hetero-dimerization (Face-3 Face-4). Alterations redox environment promote dimerization. Heterodimerization occur among between alleles different haplotypes. glycosylation differ Face-1, they may bound exogenous peptides. Spontaneous arthritis HLA-B27+ mice lacking B2m (HLA-B27+ B2m−/−) but not B2m+/− mice. HLA-B27 spontaneous configuration develop symptoms such changes nails joints, hair loss, swelling paws, leading ankyloses. Anti-HC-specific mAbs delay disease development. Some polyreactive (MEM series) used for immunostaining confirm existence several cancer cells. upregulation human cancers concomitantly downregulation intact HLAs (Face-1). monomeric dimeric interact inhibitory activating ligands KIR), growth factors, neurotransmitters. Similarities amino acid sequences HLA-II β-chain suggest could be progenitor both classes. These findings support recognition neo-HLA class proto-HLA.