Review: to what extent are T cells tolerant to immunoglobulin variable regions?
During the last 25 years it has become increasingly clear that short peptides derived from Ig V-regions are displayed on MHC class II molecules. Recognition of such idiotypic(Id)-peptide/MHC class II complexes by Id-specific CD4(+) T cells plays a role in (1) Id-driven T-B collaboration, (2) immunosurveillance of B cell cancers and (3) Id-vaccination. A crucial question is then: to what extent are T cells tolerized to Ig V-region sequences? Or rephrased: how large is the T-cell repertoire for Ig V-region sequences presented by MHC class II molecules? We argue that T cells are to a large extent tolerant to germline-encoded V-region sequences but that there is a T-cell repertoire for rare Id-sequences that arise as a consequence of somatic hyper mutation or N-region diversity. Moreover, when otherwise rare Id-sequences increase in concentration, T-cell tolerance is induced (Fig. 1). For these reasons, T cells that recognize rare Id-peptides, arising as a consequence of somatic genetic events unique to each B cell, may play a special importance in Id-driven T-B collaboration, immunosurveillance of B-cell malignancies, and Id-vaccination.
Bogen
B
B
Centre for Immune Regulation, Institute of Immunology, University of Oslo and Oslo University Hospital, Oslo, Norway. bjarne.bogen@medisin.uio.no
Ruffini
P
P
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007130:Immunoglobulin Idiotypes / Q000276:immunology / Q000378:metabolism; D007135:Immunoglobulin Variable Region / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
D000949:Histocompatibility Antigens Class II; D007130:Immunoglobulin Idiotypes; D007135:Immunoglobulin Variable Region