T Cell Tolerance to κ Light Chain (Lκ): Identification of a Naturally Processed Self-Cκ-Peptidic Region by Specific CD4+T Cell Hybridomas Obtained in Lκ-Deficient Mice

In contrast to H-2dκ light chain-deficient mice (κ−/−), BALB/c (κ+/+) mice fail to respond to κ light chains (Lκ). This suggests that Cκ-specific T cells are tolerant to this self-antigen in κ+/+mice. To get insights into the cellular and molecular basis of this tolerance, we first characterized the presented Lκ-derived Cκ-peptidic region(s). Among a library of overlapping peptides spanning the whole Cκ sequence, only three consecutive peptides are recognized by CD4+T cell hybridomas obtained in Lκ-immunized κ−/−mice. This Cκ-peptidic region, which is also the only one containing the I-Ed-binding consensus motif, is immunogenic since it is able to prime lymph node cells of κ−/−mice to subsequentin vitroproliferative response to either Lκ or κ+/+APC. Conversely, no κ+/+T cell proliferation is observed under the same conditions. Activation of our hybridomas by cells from central and peripheral lymphoid tissues reveals that this Cκ region is naturally expressed on BALB/c κ+/+APC. In addition to B cells, macrophages and dendritic cells are able to present this region. Taken together our data suggest that the described self-Cκ region is implicated in the Cκ-specific CD4+T cell tolerization in BALB/c mice.