An antibody that facilitates hematopoietic engraftment recognizes CD44.
Pretreatment of recipients with the monoclonal antibody (MoAb) S5 facilitates engraftment of bone marrow from mismatched, unrelated donors in the canine transplantation model. In the direct comparisons reported here, the S5 glycoprotein (gp) was found to have structural homology to CD44 that in humans has been implicated in adhesive interactions of one type of effector cell, the lymphocyte. The S5 antigen and gp90Hermes-1 exhibited codistribution on canine peripheral blood cells. Both S5 and Hermes-1 (anti-CD44) MoAbs recognized 90-Kd species in radioimmune precipitations of 125I surface-labeled canine peripheral blood lymphocytes and bone marrow cells. Competitive antibody binding experiments showed that the epitope detected by S5 was distinct from that bound by Hermes-1 but overlapped with those defined by two other known anti-CD44 reagents, IM7 and Hutch-1. Sequential immunoprecipitation with S5 and Hermes-1 indicated that the two antibodies recognize the same or overlapping subsets of membrane gps. Tryptic digestion of S5 and anti-CD44 immunoprecipitates generated two major iodinated peptides of 27 and 35 Kd in both cases, a further indication of structural homology. Similarly, after N-glycanase digestion, S5 and CD44 immunoprecipitates were resolved to a single 68-Kd species. These findings suggest that CD44-mediated adhesive events may affect the fate of transplanted hematopoietic cells. The previous implications of this gp in T-lymphocyte activation and lymphocyte adhesion to endothelium thus provide useful paradigms to analyze its function in the bone marrow transplant setting.
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
B M
BM
Sandmaier
R
R
Storb
F R
FR
Appelbaum
W M
WM
Gallatin
D000596:Amino Acids / Q000032:analysis; D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis / Q000276:immunology*; D000943:Antigens, Differentiation / Q000276:immunology*; D001853:Bone Marrow / Q000276:immunology; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation / Q000276:immunology* / Q000473:pathology; D004285:Dogs; D005434:Flow Cytometry; D006026:Glycoside Hydrolases / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000473:pathology; D008251:Macaca; D010449:Peptide Mapping; D011233:Precipitin Tests; D016201:Receptors, Lymphocyte Homing
D000596:Amino Acids; D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D016201:Receptors, Lymphocyte Homing; D006026:Glycoside Hydrolases; C020668:glycanase