Binding of human IgG myeloma proteins to autologous T-cell receptor determinants.
IgG myeloma proteins (MPs) produced by monoclonal plasma cells derived from B2 lymphocytes have been reported to bind to various autoantigens but the binding generally has been of low affinity. Moreover, T cells from some multiple myeloma patients can respond specifically to idiotypes of their own paraproteins. We analyzed the capacity of more than 20 human IgG MP to bind, a recombinant single-chain molecule containing complete V beta 8.1 and V alpha 1 structures, sets of synthetic peptide epitopes corresponding to a complete TCR beta chain, and a set of CDR1 epitopes corresponding to 24 human V beta gene products, and intact monoclonal T cells. Two of 20 MPs bound strongly to the recombinant TCR. Five of the same set, including these, bound to a synthetic epitope corresponding to the CDR1 segment. On a mass basis, the binding was approximately 1000-fold greater than that of pooled polyclonal IgG. The binding activity was confined to the Fab fragment and was specifically inhibitable by appropriate peptide determinants. Spectrotypic analysis using a set of CDR1 epitopes indicated that individual proteins showed characteristic binding patterns ranging from highly specific to relatively promiscuous. Highly reactive MPs also bound to TCR on intact cells in immunocytofluorescence by flow cytometry. These results are consistent with the relatively frequent occurrence of autoantibodies to TCR determinants and indicate that MPs can be derived from this autoantibody subset.
Marchalonis
J J
JJ
Department of Microbiology and Immunology, College of Medicine, University of Arizona, Tucson 85724, USA.
Garza
A
A
Landsperger
W J
WJ
Schluter
S F
SF
Wang
A C
AC
D000595:Amino Acid Sequence; D004797:Enzyme-Linked Immunosorbent Assay; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D008969:Molecular Sequence Data; D009194:Myeloma Proteins / Q000276:immunology*; D010455:Peptides / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D007074:Immunoglobulin G; D009194:Myeloma Proteins; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011994:Recombinant Proteins