HLA-F is a surface marker on activated lymphocytes

Eur J Immunol. 2010 Aug;40(8):2308-18. doi: 10.1002/eji.201040348.


Of the three nonclassical class I antigens expressed in humans, HLA-F has been least characterized with regard to expression or function. In this study, we examined HLA-F expression focusing on lymphoid cells, where our previous work with homologous cell lines had demonstrated surface HLA-F expression. HLA-F protein expression was observed by Western blot analysis in all resting lymphocytes, including B cells, T cells, NK cells, and monocytes, all of which lacked surface expression in the resting state. Upon activation, using a variety of methods to activate different lymphocyte subpopulations, all cell types that expressed HLA-F intracellularly showed an induction of surface HLA-F protein. An examination of peripheral blood from individuals genetically deficient for TAP and tapasin expression demonstrated the same activation expression profiles for HLA-F,but with altered kinetics post-activation. Further analysis of CD41+CD25+1 Treg showed that HLA-F was not upregulated on the major fraction of these cells when they were activated,whereas CD41+CD25- T cells showed strong expression of surface HLA-F when activated under identical conditions. These findings are discussed with regard to possible functions for HLA-F and its potential clinical use as a marker of an activated immune response.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • ATP-Binding Cassette Transporters / genetics
  • CD4 Antigens / biosynthesis
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Cytoplasm / metabolism
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class I / metabolism*
  • Humans
  • Immunologic Memory
  • Interleukin-2 Receptor alpha Subunit / biosynthesis
  • Lymphocyte Activation
  • Lymphocyte Subsets / immunology
  • Lymphocyte Subsets / metabolism*
  • Lymphocyte Subsets / pathology
  • Membrane Transport Proteins / deficiency
  • Membrane Transport Proteins / genetics
  • Protein Transport / immunology
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism*
  • T-Lymphocytes, Regulatory / pathology


  • ATP-Binding Cassette Transporters
  • CD4 Antigens
  • HLA-F antigens
  • Histocompatibility Antigens Class I
  • Interleukin-2 Receptor alpha Subunit
  • Membrane Transport Proteins
  • tapasin
  • transporter associated with antigen processing (TAP)