Stimulation of HLA-A,B,C by IFN-alpha. The derivation of Molt 4 variants and the differential expression of HLA-A,B,C subsets

EMBO J. 1985 Nov;4(11):2855-60. doi: 10.1002/j.1460-2075.1985.tb04014.x.


Spontaneous mutants with altered HLA-A,B,C response to interferon-alpha (IFN-alpha) were isolated from the human thymus leukemia cell line Molt 4. Using fluorescein isothiocyanate (FITC)-conjugated W6/32 (a monoclonal antibody to HLA-A,B,C) and the fluorescence-activated cell sorter, the cells with highest and lowest fluorescence after 24-48 h of IFN-alpha treatment were selected and expanded. After several cycles of selection, mutant clones with low (greater than 10% of wild-type) and high (three times better) response were obtained. A similar protocol was employed to derive high responder mutants with the monoclonal antibody YT76, which recognises a subset of HLA strongly induced by IFN-alpha. Stable clones were derived for which YT-HLA induction was 7-fold that of Molt 4 cells and for which HLA induction occurred at 100-fold lower concentrations of IFN-alpha. The high response phenotype of the mutants was not accompanied by a significant increase in the constitutive level of expression of HLA-A,B,C (in the absence of IFN). The increase in the level of HLA-A,B,C expression after IFN-alpha treatment is mostly accounted for by the increase in the expression of a subset of HLA molecules, detected by the monoclonal antibody YT76 including HLA-B molecules.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Genes / drug effects*
  • Genetic Variation*
  • HLA Antigens / genetics*
  • HLA-A Antigens
  • HLA-B Antigens
  • HLA-C Antigens
  • Humans
  • Interferon Type I / pharmacology*
  • Kinetics
  • Leukemia, Lymphoid / immunology
  • Mutation*
  • Phenotype
  • RNA, Messenger / genetics


  • HLA Antigens
  • HLA-A Antigens
  • HLA-B Antigens
  • HLA-C Antigens
  • Interferon Type I
  • RNA, Messenger