Disease relevance of HLA-F

• In this study, 10 coding sequences [hemochromatosis candidate genes (HCG) I to X] were isolated by cDNA selection using YACs covering the HLA-A/HLA-F subregion [1].
• However, extended haplotype analysis of these markers showed that a region between D6S105 and HLAF segregated with melanoma in 5/16 families [2].

High impact information on HLA-F

• The characterization of this unique HLA class I gene and the demonstration of its tissue-specific expression have prompted us to propose that HLA-5.4 be designated HLA-F [3].
• Human leukocyte antigen F (HLA-F). An expressed HLA gene composed of a class I coding sequence linked to a novel transcribed repetitive element [3].
• Consistent with a pattern of expression different from that of other class I genes, DNA sequence comparisons identified potential regulator motifs unique to HLA-5.4 and possibly essential for tissue-specific expression [3].
• The 3' untranslated region of the HLA-5.4 gene contains one member of a previously undescribed multigene family consisting of at least 30 members [3].
• Here we report the continuous 1,796,938-bp genomic sequence of the HLA class I region, linking genes between MICB and HLA-F [4].

Biological context of HLA-F

• This complex was used as an immunogen to produce a highly specific, high-affinity monoclonal antibody (FG1) that was used to study directly the cellular biology and tissue distribution of HLA-F [5].
• HLA-F tetramer binding could be conferred on non-binding cells by transfection with the inhibitory receptors ILT2 and ILT4 [5].
• In immunohistochemical study, remarkable staining for HLA-F was confirmed in EVTs throughout gestation [6].
• The haplotypes examined comprise the following highly polymorphic markers: the serological marker HLA-A and the microsatellites D6S248, D6S265, HLA-F, and D6S105 [7].
• That the currently nonessential HLA-F and MICE genes have acted as progenitors to today's immune-competent HLA-ABC and MICA/B genes provides experimental evidence for evolution by "birth and death," which has general relevance to our understanding of the evolutionary forces driving vertebrate multigene families [4].

Anatomical context of HLA-F

• Finally, using new reagents specific for HLA-F, a restricted pattern of expression was observed, primarily on extravillous trophoblasts that had invaded the maternal decidua [8].
• HLA-F could be immunoprecipitated from B cell lines and from HUT-78, a T cell line [5].
• HLA-F has a restricted pattern of tissue expression in tonsil, spleen, and thymus [5].
• HLA-F tetramers stain peripheral blood monocytes and B cells [5].
• The human class I MHC gene HLA-F is expressed in lymphocytes [9].

Regulatory relationships of HLA-F

• HLA-F is expressed as a beta2-microglobulin-associated, 42-kDa protein that shows a restricted tissue distribution [10].
• We have found that IFN-gamma treatment induces expression of HLA-F mRNA and HLA-F protein, but that this does not result in concomitant cell surface expression [10].

Other interactions of HLA-F

• In contrast, the functions of nonclassical HLA-molecules, such as HLA-E, HLA-F and HLA-G, remain to be established [11].
• We have found a considerable level of HLA-E mRNA, very low amounts of reamplified cDNA for HLA-F and both a complete lack of mRNA and reamplified cDNA for the HLA-G gene in the analyzed gametogenic cell fractions [12].
• Surface plasmon resonance studies demonstrated a direct molecular interaction of HLA-F with ILT2 and ILT4 [5].
• We have used probes from DNA within or flanking the HLA -A, -F, -G, and -7.5p genes to construct a physical linkage map that places the HLA-F, -G, and -7.5p loci in order with respect to HLA-A [13].
• HLA-F associates with at least two components of the conventional class I assembly pathway, calreticulin and TAP [10].

Analytical, diagnostic and therapeutic context of HLA-F

• The localization of HLA-F in placenta of each trimester was investigated by immunohistochemistry [6].
• Consistent with this, studies using endoglycosidase-H and cell surface immunoprecipitations also indicate that the overwhelming majority of HLA-F contains an immature oligosaccharide component and is expressed inside the cell [10].
• Whether anti-HLA-F antibodies were present in sera from cancer patients was investigated through Western blotting with recombinant HLA-F as an antigen [14].
• In addition, examination of the HLA-5.4 DNA sequence predicts that the cytoplasmic segment of this protein is shorter than that of the classical transplantation antigens [3].

References