The human class I MHC gene HLA-F is expressed in lymphocytes

Genomic and cDNA clones encoding a human, non-classical class I gene, Dew3, have been isolated. The complete coding sequence has been determined. The sequence is capable of directing expression of a protein with high sequence homology to HLA-A,B,C molecules but with a shortened cytoplasmic tail. Sequence comparisons demonstrate that this gene is from a separate locus to the 'classical' HLA-A,B,C and 'non-classical' HLA-E and HLA-G loci. Dew3 is equally distantly related to all of these previously described, functional class I genes. It is, however, extremely homologous to a third 'non-classical' gene, HLA-5.4, and to the chimpanzee gene, Ch28. The RNA species it transcribes is shorter than that of the classical genes, due to an altered acceptor splice site which results in the loss of exon 7. The transcription of Dew3 RNA shows a unique pattern of tissue distribution, being expressed in B cell lines and peripheral blood lymphocytes and absent from T cell lines, fibroblasts and a myelomonocytic leukaemia. A Dew3 protein product was detected after transfection into a human EBV-transformed B cell line but was located intracellularly. The HLA-5.4 gene has been recently designated HLA-F. The Dew3 and X5.1 clones thus represent two new alleles of the HLA-F locus in man. Sequence comparison with its chimpanzee homologue suggests that selective pressure for conservation of amino acid sequence is still maintained at this locus.