Defensins are dominant HLA-DR-associated self-peptides from CD34(-) peripheral blood mononuclear cells of different tumor patients (plasmacytoma, chronic myeloid leukemia).
The HLA-DR-associated peptides from peripheral blood mononuclear cells of 2 patients with plasmacytoma and 1 with chronic myeloid leukemia were isolated, identified, and compared. Several were identified as derivatives of the defensin family. Defensins (or human neutrophil peptides [HNP]) are antimicrobial, cationic peptides of 29 to 35 amino acids in length and are the major constituents of the azurophilic granules of human neutrophils. Using peripheral blood cells from leukapheresis, containing about 90% of polymorphonuclear cells, we could identify HNP-1, -2, and -4 and propeptides of up to 49 amino acids in length, eluted from HLA class II molecules. Binding of isolated and synthetic defensin peptides to various HLA-DR alleles using an in vitro binding/competition assay based on size exclusion chromatography revealed that defensin may bind into the peptide-binding groove. In a T-cell competition assay, defensins were able to reduce the proliferation of an HLA-DR-restricted T-cell line after preincubation of stimulating cells (CHO-DRB1*0401 transfectants) with defensin. Therefore, binding of defensins might prevent T-cell recognition of HLA class II molecules expressed on different blood precursor cells (all of which are "nonprofessional" antigen-presenting cells) by blocking the HLA peptide-binding groove or, alternatively, might protect defensin-expressing cells from self-destruction. (Blood. 2000;95:2890-2896)
Halder
T M
TM
Medical and Natural Sciences Research Center, Section for Transplantation Immunology and Immunohaematology, University of Tübingen, Tübingen, Germany.
Blüggel
M
M
Heinzel
S
S
Pawelec
G
G
Meyer
H E
HE
Kalbacher
H
H
D000595:Amino Acid Sequence; D018952:Antigens, CD34 / Q000097:blood; D001667:Binding, Competitive; D001798:Blood Proteins / Q000276:immunology*; D002850:Chromatography, Gel; D023082:Defensins; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D018922:HL-60 Cells; D006684:HLA-DR Antigens / Q000276:immunology*; D015798:HLA-DR1 Antigen / Q000276:immunology; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D007937:Leukapheresis; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000276:immunology*; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000276:immunology*; D010954:Plasmacytoma / Q000097:blood / Q000276:immunology*; D011506:Proteins / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification; D013601:T-Lymphocytes / Q000276:immunology; D023084:alpha-Defensins
D018952:Antigens, CD34; D001798:Blood Proteins; D023082:Defensins; D006684:HLA-DR Antigens; D015798:HLA-DR1 Antigen; D011506:Proteins; D023084:alpha-Defensins; C406413:human neutrophil peptide 1; D016179:Granulocyte Colony-Stimulating Factor