Differential expression of MHC class II antigens in myelomonocytic leukemia cell lines

Abstract

Major histocompatibility complex (MHC) class II antigens are discordantly expressed on hematopoietic progenitor cells. Their expression is linked to differential responsiveness of the cells to growth factors and inhibitors. We examined the expression of different MHC class II antigens in a panel of human myelomonocytic cell lines representing different stages of differentiation, by cytofluorographic analysis with monoclonal antibody (MoAb) and Northern blot analysis with specific cDNA probes. These analyses revealed discordant expression of different MHC class II antigens both in basal state and after gamma-IFN induction. Thus KG-1 myeloblast cells express all class II antigens (DR greater than DP greater than DQ) constitutively and their expression increased after gamma-IFN treatment. KG-1a, an immature blast variant of KG-1, does not express class II antigens, even after gamma-IFN treatment. THP-1, a monocytic cell line expresses DR but not DP or DQ under basal conditions. DP and DQ are, however, gamma-IFN inducible. The class II negative HL-60 promyelocytic cell line, expresses DR and DP but not DQ after gamma-IFN induction. In all the above cell lines, surface expression of class II antigens correlated with the levels of mRNA expression as determined with specific cDNA probes. In U-937, a monocytic cell line, no surface expression of class II MHC antigens was observed either with or without gamma-IFN, however, specific mRNA message was observed under basal conditions and was further increased with gamma-IFN, indicating a possible defect in assembly or transport of class II antigens. The patterns of class II MHC antigens in these leukemic cell lines may be a useful model to delineate molecular basis of discordant MHC class II expression during myelomonocytic differentiation.

Cross-linking of major histocompatibility complex class II molecules by staphylococcal enterotoxin A superantigen is a requirement for inflammatory cytokine gene expression.

“…The THP1 monocytic human cell line was obtained from American Type Culture Collection (P, ockville, MD) and maintained in P, PMI 1640 medium containing 10% FCS and antibiotics. This cell line expresses very low levels of HLA-DP, molecules, whereas it is completely negative for HLA-DQ and -DP (19). To induce high levels of M H C class II molecules, cells were stimulated with IFN-~/(50 U/ml) for 48 h. Before use, cells were washed twice with HBSS.…”

Effect of gamma interferon on HLA class‐I and ‐II transcription and protein expression in human breast adenocarcinoma cell lines

“…This discordance in expression between the 3 loci and the different cell lines may reflect a locus-independent regulation and a different degree of differentiation. It may also imply other transcriptional regulatory factors (Sugimoto et al, 1989;Yunis et al, 1989).…”

“…In most reports, I F N y appeared to induce expression of HLA-DR, DP and, to a lesser extent, DQ determinants. The DQ locus was not induced in a promyelocytic cell line HL-60, nor in neuroblastoma cell lines (Sugimoto et al, 1989;Yunis et al, 1989). In one melanoma cell line (M14) the DQ locus was very sensitive to IFN-y treatment.…”

Detection of Established and Novel Alleles of the HLA‐DPB1 Locus by PCR‐SSO

“…The HLA-DP genes occur at the centromeric border of the HLA class 11 gene complex on the short arm of chromosome 6 [ 11. HLA-DPA1 and HLA-DPB1 genes encode the aand @-chains of heterodimeric DP molecules, which are displayed on the surface of distinct cell types either constitutively or upon induction by interleukins [2]. HLA-DP molecules have been discovered by cellular typing techniques (31.…”