HLA class I chromosomal region, genes, and products: facts and questions

Among the various areas of recent investigation in the field of human MHC class I antigens, the following have been selected for discussion in this review: (1) classical HLA class I genes: are they ubiquitously expressed?, what are the special features of their polymorphism?, are HLA-C molecules functional?, (2) non-classical HLA class I gene products: how restricted is their tissue distribution?, do they exhibit a little polymorphism?, what is their function, if any? (3) non-HLA genes recently detected in the HLA class I chromosomal region: are some of them involved in immunological function and development?, (4) other novel coding sequences present, or possibly present, in the region: the hemochromatosis gene, grc region and associated tumor suppressor genes, housekeeping genes, human equivalent of the murine H-2M region and Ped gene; (5) transcriptional regulation: are there cis-regulatory elements, including locus control region(s), located elsewhere than in the promoters? are CpG methylation, gene imprinting, chromatin structure, DNA rearrangement also implicated? what are the transcription factors involved and how do they interact with each other? is there HLA class I locus-, allele-, or isoform-specific regulation? is class I gene expression dysregulated in human tumors? The answers to these questions are crucial for the development of the future directions for research.