HLA non-A,B,C class I genes: their structure and expression.
Clearly, the human genome includes a group of genes closely related to but distinct from the HLA class I genes encoding the HLA-A, -B, and -C major transplantation antigens. These non-A,B,C class I genes, designated as HLA-E, HLA-F, and HLA-G, are on the short arm of chromosome 6 and part of the HLA class I gene family. Although the human HLA-E, -F, and -G genes have features in common with the murine Qa- and Tla-genes, e.g. little allelic polymorphism, their relationship to the murine Qa- and Tla-region genes remains unclear. It has been suggested that the nonclassical MHC class I molecules function as ligands for gamma-delta T lymphocytes. The speculation is supported by the recent reports of a murine Qa-1 restricted gamma-delta T cell hybridoma and recognition of a TL antigen by gamma delta T cell receptors. The amino acid sequences of the HLA-E, -F, and -G encoded proteins suggest that each protein is likely to fold three-dimensionally into a structure very similar to HLA-A2 and has a capability of presenting a bound peptide at the cell surface. In light of the possible role of bound peptide in the expression of a class I molecule at the cell surface, it is interesting to note that the HLA-E and HLA-F molecules, even in association with beta 2-microglobulin, could not be detected at the cell surface of a transfected B-LCL. In contrast, the HLA-G molecule was found at the surface of transfected B-LCLs. Both HLA-E and HLA-F are less similar in sequence to HLA-A,B,C than is HLA-G. One explanation would be that the HLA-E and -F molecules have a mutation such that they are no longer able to bind peptide. If the HLA-G molecule does function to present peptide to T lymphocytes, there are features unique to HLA-G that should impact on its ability to perform this function. Both the analysis of HLA-G RNA and protein in trophoblasts indicate that HLA-G, unlike HLA-A, -B, -C, is relatively nonpolymorphic. Since HLA-A,B,C polymorphism is thought to increase the number of different peptides that these molecules can bind, HLA-G is likely to be able to bind a relatively limited variety of peptides. HLA-G also differs from HLA-A, -B, and -C in that it seems to only be expressed by placental amniochorionic trophoblasts.(ABSTRACT TRUNCATED AT 400 WORDS)
Heinrichs
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Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis.
Orr
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D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002896:Chromosomes, Human, Pair 6; D016384:Consensus Sequence; D005786:Gene Expression Regulation; D005805:Genes, MHC Class I; D006680:HLA Antigens / Q000235:genetics* / Q000276:immunology; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009928:Organ Specificity; D011544:Pseudogenes; D012045:Regulatory Sequences, Nucleic Acid; D012689:Sequence Homology, Nucleic Acid; D000097625:HLA-E Antigens
D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D000097625:HLA-E Antigens; C062341:HLA-F antigens