Cerebrospinal fluid T cell clones from patients with multiple sclerosis: Recognition of idiotopes on monoclonal IgG secreted by autologous cerebrospinal fluid B cells

Abstract

Due to somatic recombination and hypermutation, Ig variable heavy (VH) and light (VL) regions contain unique immunogenic determinants, idiotopes (Id), which can stimulate T cells. To address the relevance of this in a human disease, monoclonal IgG (mAb)-secreting B cell clones were established from the cerebrospinal fluid (CSF) of two patients with multiple sclerosis (MS). HLA-DR-restricted CD4+ T cell lines and clones from CSF of both patients specifically recognized autologous CSF mAb. The CSF T cell clones produced IFN-γ; some also produced TNF-α, IL-10 and IL-5. VH and VL on the monoclonal IgG derived from CSF B cells expressed amino acid replacements due to somatic mutations. A T cell epitope was mapped to a VH framework region, where an amino acid replacement was critical for the T cell recognition. The finding of Id-specific T cells and Id-bearing B cells in the CSF indicates that they coexist within the diseased organ, and provide a basis for the study of Id-driven T-B cell collaboration in a human autoimmune disease. © 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.