T cell tolerance to kappa light chain (L kappa): identification of a naturally processed self-C kappa-peptidic region by specific CD4+ T cell hybridomas obtained in L kappa-deficient mice.
In contrast to H-2d kappa light chain-deficient mice (kappa-/-), BALB/c (kappa+/+) mice fail to respond to kappa light chains (L kappa). This suggests that C kappa-specific T cells are tolerant to this self-antigen in kappa+/+ mice. To get insights into the cellular and molecular basis of this tolerance, we first characterized the presented L kappa-derived C kappa-peptidic region(s). Among a library of overlapping peptides spanning the whole C kappa sequence, only three consecutive peptides are recognized by CD4+ T cell hybridomas obtained in L kappa-immunized kappa-/- mice. This C kappa-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 kappa-/- mice to subsequent in vitro proliferative response to either L kappa or kappa+/+ APC. Conversely, no kappa+/+ T cell proliferation is observed under the same conditions. Activation of our hybridomas by cells from central and peripheral lymphoid tissues reveals that this C kappa region is naturally expressed on BALB/c kappa+/+ 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-C kappa region is implicated in the C kappa-specific CD4+ T cell tolerization in BALB/c mice.
Faure
M
M
Département d'Immunologie, Institut Pasteur, Paris, France. mfaure@pasteur.fr
Sanchez
P
P
Cazenave
P A
PA
Rueff-Juy
D
D
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D000939:Epitopes; D005260:Female; D006183:H-2 Antigens; D006825:Hybridomas; D007108:Immune Tolerance; D007145:Immunoglobulin kappa-Chains / Q000235:genetics / Q000276:immunology*; D008221:Lymphoid Tissue / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*; D013045:Species Specificity
D000939:Epitopes; D006183:H-2 Antigens; D007145:Immunoglobulin kappa-Chains; D010446:Peptide Fragments