Antigen presentation by T cells: T cell receptor ligation promotes antigen acquisition from professional antigen‐presenting cells

Abstract

The purpose of this study was to determine whether the clonotypic specificity of the T cell receptor influences the specificity of T cell-mediated antigen presentation. We have previously shown that myelin basic protein (MBP)-specific Lewis rat GP2.E5/R1 (R1) T cells cultured with antigen, irradiated syngeneic splenocytes (IrrSPL) and tolerogenic monoclonal antibody become highly effective antigen-presenting cells (APC). In the current studies, we investigated the transfer of specific (MBP) and unrelated (conalbumin) antigens from antigen-pulsed SPL to R1 T cells. R1 T cells cultured with IrrSPL that were pulsed simultaneously with both MBP and conalbumin acquired and presented both antigens to the appropriate T cell responders in a secondary assay. These results suggested a physical transfer of major histocompatibility complex (MHC)/peptide complexes from professional APC to R1 T cells. Transfer of conalbumin from professional APC to R1 T cells required specific recognition of MBP and was optimal when both conalbumin and MBP were presented on the same group of professional APC. Antigens transfer did not occur when allogeneic SPL were used as APC. The anti-I-A mAb OX6 inhibited antigen transfer but only when added during the initiation of culture. OX6 also inhibited antigen acquisition by R1-trans, a variant of the R1 T cell line which constitutively synthesizes high levels of I-A, from MBP-pulsed IrrSPL but blockade of I-A did not inhibit antigen acquisition when soluble MBP was added directly to the culture. Despite constitutive synthesis of I-A, R1-trans T cells did not acquire guinea pig MBP from pulsed allogeneic APC. These studies demonstrate that although T cells of a particular specificity can present unrelated antigens, the cognate interaction of the T cell antigen receptor with the appropriate antigen/self-MHC complex strongly promotes acquisition of these complexes from professional APC.

IL-2/Neuroantigen Fusion Proteins as Antigen-Specific Tolerogens in Experimental Autoimmune Encephalomyelitis (EAE): Correlation of T Cell-Mediated Antigen Presentation and Tolerance Induction

“…R1-trans T cells constitutively synthesized MHCII (14,24,40,41), and RsL.11 T cells that were activated with GPMBP in the presence of irradiated splenic APC also synthesized MHCII (42). Thus, in cultures of R1-trans T cells and RsL.11 responders (Fig.…”

Type 1 IFN Maintains the Survival of Anergic CD4+ T Cells

“…In addition, activated T cells can actively acquire MHC/ peptide complexes from APCs, which can then be presented to other specific T cells (32,33), and this may be associated with the induction of tolerance (33). Furthermore, T cells themselves may process and present Ag under certain conditions (34).…”

Intercellular Trogocytosis Plays an Important Role in Modulation of Immune Responses

“…Of late new reports of intercellular membrane transfer started pouring in. It was demonstrated that T cells can acquire not only the MHC class I and class II proteins (18,19), but also the costimulatory proteins (20)(21)(22), the membrane fragments (23,24) from APCs and the proteins from endothelial cells (25). Till recently, the protein transfer by trogocytosis is believed to be unidirectional in murine system (1).…”

“…The peptide-MHC complexes transferred from APCs to T cells are the best studied examples of protein transfer that occurs via trogocytosis. Here, T cells can acquire both MHC class I and class II proteins from APCs (19,23,24,(53)(54)(55). Reports of intercellular transfer of membrane fragments from APCs to T cells (24,54) and from target cells to NK cells (31), and even through homotypic interactions between cells like Daudi cells (56), are consistent with the membrane transfer mechanism that involves the transfer of membrane fragments derived from the intercellular contact or IS (57).…”