T cell recognition of somatically-generated Ab diversity.
During an immune response, specific Abs and B cells that are infrequently represented in the preimmune repertoire become amplified to abundance. Novel structures are also created through the physiological process of somatic hypermutation in Ab genes. This presents a challenge for T cell self-tolerance, because many potential V region epitopes are either rare or nonexistent during the maturation of the T cell repertoire in the thymus. To explore the potential for T cell recognition of Ab V regions, we immunized A/J mice with two somatically mutated mAbs (mAb36-71 and mAb45-49) derived from A/J mice and produced 13 mAb-specific T cell hybridomas. All of the T cell hybridomas express alpha beta receptors and CD4, and their responses to the mAb are restricted in the context of class II MHC glycoproteins. In presentation studies with fixed APCs and whole or trypsinized mAb, we found that processing of the mAb is necessary for stimulation of the T cell hybridomas. Therefore each of the hybridomas recognizes the mAbs in a conventional class II MHC-restricted manner. We also found that each of the 13 T cell hybridomas responded to the somatically-mutated light chains of mAb45-49 and mAb36-71. In contrast, none of them responded to unmutated versions of the same light chains. These results show that the T cell repertoire includes members able to recognize syngeneic Abs containing somatic mutations that were physiologically acquired during the course of an immune response.
Eyerman
M C
MC
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
Wysocki
L
L
D000595:Amino Acid Sequence; D000818:Animals; D000916:Antibody Diversity; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006825:Hybridomas / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010446:Peptide Fragments / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000949:Histocompatibility Antigens Class II; D007135:Immunoglobulin Variable Region; D010446:Peptide Fragments