Soluble form of an HLA-B7 class I antigen specifically suppresses humoral alloimmunization.
A soluble HLA-B7 molecule, designated sB7 and generated by genetically engineering the B7 gene to remove the transmembrane and cytoplasmic domains, was tested as a tolerogen. Supernatants from cultures of C1R cells transfected with the gene for sB7 were harvested and concentrated, as were control supernatants. From days -17 to -1, C57Bl/6 mice were pretreated with a total of 11 intraperitoneal doses of 1.0 microgram each of sB7 or appropriate control supernatant, and then were challenged intraperitoneally on each of days 0, 7, and 14 with 10(6) C1R-B7 cells (expressing surface HLA-B7). Antibody kinetics revealed (1) anti-B7 was not induced after sB7 pretreatment; (2) the anti-B7 response of sB7-pretreated mice was marginal and of apparent low avidity compared with the brisk anti-B7 response of control mice; (3) none of the mice made antibody to a control HLA antigen, A24; (4) all mice made strong antibody responses to the non-B7 surface antigens of C1R; (5) free sB7 did not appear in the blood of the treated mice; and (6) all mice appeared to be generally healthy. These data show soluble B7 antigen is not immunogenic and appears to specifically block humoral immune response to cell membrane-bound HLA-B7 in a nontoxic manner.
Grumet
F C
FC
Department of Pathology, Stanford University School of Medicine, California.
Krishnaswamy
S
S
See-Tho
K
K
Filvaroff
E
E
Hiraki
D D
DD
D000818:Animals; D005260:Female; D005347:Fibroblasts; D005434:Flow Cytometry; D015793:HLA-B7 Antigen / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007114:Immunization; D007074:Immunoglobulin G / Q000032:analysis; D007518:Isoantibodies / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000276:immunology; D012995:Solubility; D014162:Transfection
D015793:HLA-B7 Antigen; D007074:Immunoglobulin G; D007518:Isoantibodies; D011994:Recombinant Proteins