An important and yet unresolved question concerns the mode of T cell recognition of idiotypic
epitopes on
immunoglobulin molecules in humans. Results from murine and human studies show that some idiotype-specific T cells recognize conformational
epitopes on
immunoglobulin, and such T cells are not MHC-restricted. In the present study T cell stimulation induced by idiotypic determinants on the autologous monoclonal
IgG (
M-components) from patients with
monoclonal gammopathies was studied. In parallel, T cell stimulation in response to a conventional
antigen, purified
protein derivative, was also examined. It is shown that, as with conventional
antigen, idiotype-induced T cell stimulation requires the presence of antigen-presenting cells (APC; monocytes and/or B cells), and is MHC class II (DR)-restricted. B cells, but not monocytes, can present idiotypic determinants to T cells at very low
antigen concentrations, while monocytes do so only when
antigen is present at high concentrations. Antigen processing and presentation is abrogated by treatment of APC with
chloroquine. In conclusion, our study demonstrates that human idiotype-specific T cells recognize processed idiotypic determinants presented by MHC class II (
HLA-DR) molecules on APC, and that B cells require about 1000-fold less
antigen that monocytes.