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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.
Author(s) -
Burrone O.R.,
Kefford R.F.,
Gilmore D.,
Milstein C.
Publication year - 1985
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1985.tb04014.x
Subject(s) - biology , stimulation , human leukocyte antigen , hla b antigens , differential (mechanical device) , alpha (finance) , immunology , genetics , microbiology and biotechnology , antigen , neuroscience , physics , medicine , construct validity , nursing , patient satisfaction , thermodynamics
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.