Briefly reviewing the literature on HLA-I isoforms in bony fishes, sharks, amphibians, reptiles, birds, and mammals and during vertebrate evolution (see reference 1, 194–206 in [4]) and based on the findings that inflammation, autoimmune diseases, and human cancers promote de novo expression of Face-2 and trigger further the formation of noncovalent transient HC-dimers (Face-3 and Face-4), we coined the term “Proto-HLA” for these different forms of B2m-free HCs (Face-2–4). This evidence concerns the gene RCE1 and cancer.