细胞表面的HLA-I分子（面-1）由一个多肽重链（HC）和两个凹槽结构域（G区域）以及一个恒定域（C-区域）组成，还有一个轻链B2-微球蛋白（B2m）。然而，HCs也可以独立地在细胞表面上无肽酶地展开成B2m-无肽酶的HC单体（面-2）、B2m-无肽酶的HC二聚体（面-3）和B2m-无肽酶的HC异二聚体（面-4）。通过抗病毒抗生素引发新合成蛋白质从内质网（ER）释放被确认这些HLA变异体的运输从ER到细胞表面。在肺、支气管、表皮、食管、乳房、胃、回肠、结肠、胆囊、尿膀胱、精囊卵巢上皮、子宫内膜、胸腺、脾脏和淋巴细胞正常细胞表面低水平发生面-2。它们在免疫细胞上通过促炎细胞因子、抗CD3抗体、抗生素（如离子霉素）、植物血凝素、维甲酸和磷酸酯增强。只要细胞保持活化状态，它们在细胞表面的密度就保持较高。在活化诱导的上调后，面-2分子会发生同聚和异聚（面-3和面-4）。氧化还原环境的变化促进二聚化。异聚化可在不同单倍基因型的等位基因之间和之间发生。这些变异体的糖基化与面-1不同，并且可能与结合的外源性肽发生。缺少B2m的HLA-B27阳性小鼠（HLA-B27 + B2m-/-）会出现自发性关节炎，而HLA-B27 + B2m+/-小鼠则不会。处于面-2自发配置的小鼠会出现指甲和关节的改变、脱发以及爪子肿胀，导致强直性。抗HC特异性mAb能延缓疾病发展。用于免疫染色的一些HLA-I多反应性mAb（MEM系列）证实在多种癌细胞中存在B2m-无肽酶的变异体。人类癌症中面-2的上调与完整HLAs（面-1）的下调同时发生。HLA单体和二聚体变异体与抑制性和激活性配体（例如KIR）、生长因子、细胞因子和神经递质相互作用。HLA-I变异体和HLA-II β链氨基酸序列的相似性表明面-2可能是HLA类的原型。这些发现可能支持将这些变异体识别为新的HLA类和原HLA类。

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