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Gene Review

HLA-F  -  major histocompatibility complex, class I, F

Homo sapiens

Synonyms: CDA12, HLA F antigen, HLA class I histocompatibility antigen, alpha chain F, HLA-5.4, HLA-CDA12, ...
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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


Regulatory relationships of HLA-F


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].


  1. Structural analysis of the HLA-A/HLA-F subregion: precise localization of two new multigene families closely associated with the HLA class I sequences. Pichon, L., Carn, G., Bouric, P., Giffon, T., Chauvel, B., Lepourcelet, M., Mosser, J., Legall, J.Y., David, V. Genomics (1996) [Pubmed]
  2. Linkage analysis in familial melanoma kindreds to markers on chromosome 6p. Walker, G.J., Nancarrow, D.J., Walters, M.K., Palmer, J.M., Weber, J.L., Hayward, N.K. Int. J. Cancer (1994) [Pubmed]
  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. Geraghty, D.E., Wei, X.H., Orr, H.T., Koller, B.H. J. Exp. Med. (1990) [Pubmed]
  4. Molecular dynamics of MHC genesis unraveled by sequence analysis of the 1,796,938-bp HLA class I region. Shiina, T., Tamiya, G., Oka, A., Takishima, N., Yamagata, T., Kikkawa, E., Iwata, K., Tomizawa, M., Okuaki, N., Kuwano, Y., Watanabe, K., Fukuzumi, Y., Itakura, S., Sugawara, C., Ono, A., Yamazaki, M., Tashiro, H., Ando, A., Ikemura, T., Soeda, E., Kimura, M., Bahram, S., Inoko, H. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  5. Functional characterization of HLA-F and binding of HLA-F tetramers to ILT2 and ILT4 receptors. Lepin, E.J., Bastin, J.M., Allan, D.S., Roncador, G., Braud, V.M., Mason, D.Y., van der Merwe, P.A., McMichael, A.J., Bell, J.I., Powis, S.H., O'Callaghan, C.A. Eur. J. Immunol. (2000) [Pubmed]
  6. Human Leukocyte Antigen F Protein is Expressed in the Extra-Villous Trophoblasts but Not on the Cell Surface of them. Nagamatsu, T., Fujii, T., Matsumoto, J., Yamashita, T., Kozuma, S., Taketani, Y. Am. J. Reprod. Immunol. (2006) [Pubmed]
  7. Haplotype analysis in Australian hemochromatosis patients: evidence for a predominant ancestral haplotype exclusively associated with hemochromatosis. Jazwinska, E.C., Pyper, W.R., Burt, M.J., Francis, J.L., Goldwurm, S., Webb, S.I., Lee, S.C., Halliday, J.W., Powell, L.W. Am. J. Hum. Genet. (1995) [Pubmed]
  8. Protein expression and peptide binding suggest unique and interacting functional roles for HLA-E, F, and G in maternal-placental immune recognition. Ishitani, A., Sageshima, N., Lee, N., Dorofeeva, N., Hatake, K., Marquardt, H., Geraghty, D.E. J. Immunol. (2003) [Pubmed]
  9. The human class I MHC gene HLA-F is expressed in lymphocytes. Lury, D., Epstein, H., Holmes, N. Int. Immunol. (1990) [Pubmed]
  10. HLA-F is a predominantly empty, intracellular, TAP-associated MHC class Ib protein with a restricted expression pattern. Wainwright, S.D., Biro, P.A., Holmes, C.H. J. Immunol. (2000) [Pubmed]
  11. Nonclassical HLA-G molecules are classical peptide presenters. Diehl, M., Münz, C., Keilholz, W., Stevanović, S., Holmes, N., Loke, Y.W., Rammensee, H.G. Curr. Biol. (1996) [Pubmed]
  12. Analysis of HLA class Ib gene expression in male gametogenic cells. Fiszer, D., Ulbrecht, M., Fernandez, N., Johnson, J.P., Weiss, E.H., Kurpisz, M. Eur. J. Immunol. (1997) [Pubmed]
  13. A physical linkage map of HLA-A, -G, -7.5p, and -F. Schmidt, C.M., Orr, H.T. Hum. Immunol. (1991) [Pubmed]
  14. Detection of anti-HLA-F antibodies in sera from cancer patients. Noguchi, K., Isogai, M., Kuwada, E., Noguchi, A., Goto, S., Egawa, K. Anticancer Res. (2004) [Pubmed]
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