APCs Present Aβk-Derived Peptides That Are Autoantigenic to Type B T Cells

Abstract

Type B T cells recognize peptide provided exogenously but are ignorant of the same epitope derived from intracellular processing. In this study, we demonstrate the existence of type B T cells to an abundant autologous peptide derived from processing of the I-Ak β-chain. T cell hybridomas raised against this peptide fail to recognize syngeneic APC despite abundant presentation of the naturally processed epitope but react in a dose-dependent manner to exogenous peptide. Moreover, these hybridomas respond to Aβk peptide extracted from the surface of I-Ak-expressing APC. This peptide was isolated from B cell lines where it was found in high abundance; it was also present in lines lacking HLA-DM, but in considerably lower amounts. Therefore, type B T cells exist in the naive repertoire to abundant autologous peptides. We discuss the implications of these findings to the potential biological role of type B T cells in immune responses and autoimmune pathology.

Cutting Edge: H-2DM Is Responsible for the Large Differences in Presentation Among Peptides Selected by I-Ak During Antigen Processing

“…In experiments in progress we are reporting on the content and features of peptides bound to I-A k in T1.A k and T2.A k examined by tandem electrospray mass spectrometry. In our previous analysis of one peptide family presented by I-A k (derived from the I-A k ␤-chain), we found reduced abundance of this high affinity peptide family on T2.A k relative to T1.A k (26). The biochemical results were confirmed by functional assays.…”

B cell antigen presentation is sufficient to drive neuro-inflammation in an animal model of multiple sclerosis

“…The generation of the MOG-specific T cell hybridoma 204.62 was performed according to standard protocol (31). Briefly, B6 mice were immunized via footpad injection of 10 nM of MOG emulsified in CFA (Difco, Detroit, MI).…”

“…A total of 5×10 5 APCs were cultured with 5×10 4 hybridoma cells with antigen overnight at 37C. Proliferation of CTLL-2 was measured after addition of supernatant by [ 3 H]thymidine incorporation as described (31). EC 50 was calculated by constructing a dose-response curve for each population of APCs, using the concentration of rMOG providing half-maximal IL-2 response by the hybridoma 204.62.…”

“…Briefly, B6 mice were immunized via footpad injection of 10 nM of MOG emulsified in CFA (Difco, Detroit, MI). Seven days following immunization, the draining popliteal lymph nodes were dispersed and fused according to standard protocols (31). Hybridomas were used in antigen presentation assays according to prior reports (25).…”

Amino-Terminal Flanking Residues Determine the Conformation of a Peptide–Class II MHC Complex

“…This phenomenon was first observed in studies of a so-called cryptic epitope (4) but has since been observed with regard to a variety of epitopes and MHC molecules and appears to be a general feature of class II MHC-peptide interaction (5)(6)(7)(8). Selfreactive type B T cells escape negative selection under conditions in which type A T cells are deleted in the thymus, suggesting that they may play a role in autoimmunity (9,10). Furthermore, a subset of type B T cells recognize peptides as short as seven residues; we speculate that these may be involved in host defense, responding to short peptides of microbial origin (11).…”