HLA-F is a predominantly empty, intracellular, TAP-associated MHC class Ib protein with a restricted expression pattern

J Immunol. 2000 Jan 1;164(1):319-28. doi: 10.4049/jimmunol.164.1.319.


HLA-F is currently the most enigmatic of the human MHC-encoded class Ib genes. We have investigated the expression of HLA-F using a specific Ab raised against a synthetic peptide corresponding to amino acids 61-84 in the alpha1 domain of the predicted HLA-F protein. HLA-F is expressed as a beta2-microglobulin-associated, 42-kDa protein that shows a restricted tissue distribution. To date, we have detected this product only in peripheral blood B cells, B cell lines, and tissues containing B cells, in particular adult tonsil and fetal liver, a major site of B cell development. Thermostability assays suggest that HLA-F is expressed as an empty heterodimer devoid of peptide. 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. 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. HLA-F associates with at least two components of the conventional class I assembly pathway, calreticulin and TAP. The unusual characteristics of the predicted peptide-binding groove together with the predominantly intracellular localization raise the possibility that HLA-F may be capable of binding only a restricted set of peptides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 2
  • ATP-Binding Cassette Transporters / metabolism*
  • Adult
  • Amino Acid Sequence
  • Antigen Presentation
  • Cell Line
  • Gene Expression Regulation / immunology
  • HLA Antigens / biosynthesis*
  • HLA Antigens / genetics
  • HLA Antigens / isolation & purification*
  • HLA Antigens / metabolism
  • Histocompatibility Antigens Class I / biosynthesis*
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / isolation & purification*
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Interferon-gamma / pharmacology
  • Intracellular Fluid / immunology*
  • Intracellular Fluid / metabolism*
  • Jurkat Cells
  • Molecular Sequence Data
  • Organ Specificity / immunology
  • Peptides / immunology
  • Peptides / metabolism
  • Protein Binding / immunology
  • Tumor Cells, Cultured


  • ATP Binding Cassette Transporter, Subfamily B, Member 2
  • ATP-Binding Cassette Transporters
  • HLA Antigens
  • HLA-F antigens
  • Histocompatibility Antigens Class I
  • Peptides
  • TAP1 protein, human
  • Interferon-gamma