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Monoclonal antibodies to HLA-DP, DQ, and DR determinants: functional effects on the activation and proliferation of normal and EBV-transformed B cells.
Exp Hematol. 1986 Oct; 14(9):887-95.EH

Abstract

To investigate the function of HLA class II molecules in B-cell activation, we generated three new anti-HLA class II monoclonal antibodies with differing specificities for DP, DQ, and DR determinants. These were tested for their ability to inhibit various B- and T-lymphocyte responses. Each of these antibodies (NB-29, DH-84, and DH-224) immunoprecipitates a heterodimer of approximately 35,000 and 28,000 mol wt from 125I-surface-labeled B-lymphoma cells, as shown by SDS-PAGE. NB-29 (IgG1) detects a polymorphic DQ determinant, while DH-224 (IgG1) is reactive with monomorphic DR determinants, and DH-84 (IgG2a) has specificity for DP, DQ, and DR. Both DH-224 and DH-84, but not NB-29, were found to inhibit significantly the stimulation of peripheral blood mononuclear cells (PBMC) by anti-mu (70%-90% inhibition) and by lipopolysaccharide (80%-90% inhibition), as measured by incorporation of tritiated thymidine. When added to highly purified populations of peripheral blood B cells, none of these anti-class II monoclonal antibodies inhibited anti-mu-induced stimulation. This suggests that the inhibitory effect that DH-224 and DH-84 have on the stimulation of unfractionated PBMC may be due to their ability to interfere with the action of accessory cells. Epstein-Barr-virus (EBV)-transformed B-cell lines, in contrast, showed substantial inhibition of growth when cultured in the presence of any of the three antibodies. With respect to T cells, DH-84 and DH-224 strongly inhibited the mixed lymphocyte response; NB-29 did not. None of these antibodies inhibited stimulation of PBMC by phytohemagglutinin (PHA). These findings suggest that DQ and DR HLA class II molecules have differing roles in B-cell activation and document a direct antiproliferative effect of anti-HLA class II monoclonal antibodies on the growth of EBV-transformed cell lines.

Authors

No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

2428652

Citation

Howard, D R., et al. "Monoclonal Antibodies to HLA-DP, DQ, and DR Determinants: Functional Effects On the Activation and Proliferation of Normal and EBV-transformed B Cells." Experimental Hematology, vol. 14, no. 9, 1986, pp. 887-95.
Howard DR, Eaves AC, Takei F. Monoclonal antibodies to HLA-DP, DQ, and DR determinants: functional effects on the activation and proliferation of normal and EBV-transformed B cells. Exp Hematol. 1986;14(9):887-95.
Howard, D. R., Eaves, A. C., & Takei, F. (1986). Monoclonal antibodies to HLA-DP, DQ, and DR determinants: functional effects on the activation and proliferation of normal and EBV-transformed B cells. Experimental Hematology, 14(9), 887-95.
Howard DR, Eaves AC, Takei F. Monoclonal Antibodies to HLA-DP, DQ, and DR Determinants: Functional Effects On the Activation and Proliferation of Normal and EBV-transformed B Cells. Exp Hematol. 1986;14(9):887-95. PubMed PMID: 2428652.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Monoclonal antibodies to HLA-DP, DQ, and DR determinants: functional effects on the activation and proliferation of normal and EBV-transformed B cells. AU - Howard,D R, AU - Eaves,A C, AU - Takei,F, PY - 1986/10/1/pubmed PY - 1986/10/1/medline PY - 1986/10/1/entrez SP - 887 EP - 95 JF - Experimental hematology JO - Exp Hematol VL - 14 IS - 9 N2 - To investigate the function of HLA class II molecules in B-cell activation, we generated three new anti-HLA class II monoclonal antibodies with differing specificities for DP, DQ, and DR determinants. These were tested for their ability to inhibit various B- and T-lymphocyte responses. Each of these antibodies (NB-29, DH-84, and DH-224) immunoprecipitates a heterodimer of approximately 35,000 and 28,000 mol wt from 125I-surface-labeled B-lymphoma cells, as shown by SDS-PAGE. NB-29 (IgG1) detects a polymorphic DQ determinant, while DH-224 (IgG1) is reactive with monomorphic DR determinants, and DH-84 (IgG2a) has specificity for DP, DQ, and DR. Both DH-224 and DH-84, but not NB-29, were found to inhibit significantly the stimulation of peripheral blood mononuclear cells (PBMC) by anti-mu (70%-90% inhibition) and by lipopolysaccharide (80%-90% inhibition), as measured by incorporation of tritiated thymidine. When added to highly purified populations of peripheral blood B cells, none of these anti-class II monoclonal antibodies inhibited anti-mu-induced stimulation. This suggests that the inhibitory effect that DH-224 and DH-84 have on the stimulation of unfractionated PBMC may be due to their ability to interfere with the action of accessory cells. Epstein-Barr-virus (EBV)-transformed B-cell lines, in contrast, showed substantial inhibition of growth when cultured in the presence of any of the three antibodies. With respect to T cells, DH-84 and DH-224 strongly inhibited the mixed lymphocyte response; NB-29 did not. None of these antibodies inhibited stimulation of PBMC by phytohemagglutinin (PHA). These findings suggest that DQ and DR HLA class II molecules have differing roles in B-cell activation and document a direct antiproliferative effect of anti-HLA class II monoclonal antibodies on the growth of EBV-transformed cell lines. SN - 0301-472X UR - https://www.unboundmedicine.com/medline/citation/2428652/Monoclonal_antibodies_to_HLA_DP_DQ_and_DR_determinants:_functional_effects_on_the_activation_and_proliferation_of_normal_and_EBV_transformed_B_cells_ L2 - https://antibodies.cancer.gov/detail/CPTC-HLA-DPB1-2 DB - PRIME DP - Unbound Medicine ER -