Antibodies to a conserved region of HLA class I molecules, capable of modulating CD8 T cell-mediated function, are present in pooled normal immunoglobulin for therapeutic use.
Intravenous immunoglobulin (IVIg) is increasingly used for the treatment of autoimmune diseases and the prevention of infections and of graft versus host reactions in recipients of allogeneic bone marrow transplants. The immunomodulatory effects of IVIg are largely dependent on their ability to interact with membrane molecules of lymphocytes. We report here that IVIg recognizes the B07.75-84 peptide, corresponding to a conserved region of the alpha I helix of the first domain of HLA-B7 01, which represents a nonpolymorphic determinant of HLA class I molecules. Intact IVIg and its F(ab')2 fragments bound to the peptide as well as to purified soluble HLA and to HLA on a human T cell line. Binding of IVIg to HLA was assessed by ELISA, immunofluorescence, and real-time analysis of the interaction using the BIAlite system. The binding of antipeptide antibodies to HLA was inhibited by free peptide. Antipeptide antibodies isolated from IVIg by affinity chromatography inhibited CD8 cell-mediated cytotoxicity of an influenza virus-specific human T cell line. The presence in IVIg of antibodies to critical regions of HLA class 1 molecules suggests a possible role for IVIg in modulation of class-I-restricted cellular interactions in the immune response.
Kaveri
S
S
Institut National de la Santé et de la Recherche Médicale U430, Hôpital Broussais, Paris, France.
Vassilev
T
T
Hurez
V
V
Lengagne
R
R
Lefranc
C
C
Cot
S
S
Pouletty
P
P
Glotz
D
D
Kazatchkine
M D
MD
D000595:Amino Acid Sequence; D000918:Antibody Specificity; D001327:Autoimmune Diseases / Q000628:therapy; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects*; D017124:Conserved Sequence; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D006086:Graft vs Host Disease / Q000517:prevention & control; D015793:HLA-B7 Antigen / Q000235:genetics / Q000276:immunology*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology*
D015793:HLA-B7 Antigen; D016756:Immunoglobulins, Intravenous; D010446:Peptide Fragments