Presentation of acquired peptide-MHC class II ligands by CD4+ regulatory T cells or helper cells differentially regulates antigen-specific CD4+ T cell response

• Published in: The Journal of immunology (1950) 2011-02, Vol.186 (4), p.2148-2155
• Main Authors: Zhou, Gang, Ding, Zhi-Chun, Fu, Jie, Levitsky, Hyam I
• Format: Article
• Language: English
• Subjects: Animals; Antigen Presentation - immunology; Antigen-Presenting Cells - immunology; Antigen-Presenting Cells - metabolism; Antigen-Presenting Cells - pathology; CD4 Antigens - biosynthesis; CD4 Antigens - physiology; Cell Line, Tumor; Chickens; Epitopes, T-Lymphocyte - immunology; Histocompatibility Antigens Class II - immunology; Histocompatibility Antigens Class II - metabolism; Immunologic Memory; Ligands; Lymphocyte Activation - immunology; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Transgenic; Peptides - immunology; Peptides - metabolism; Protein Interaction Mapping; Sarcoma, Experimental - immunology; Sarcoma, Experimental - metabolism; Sarcoma, Experimental - pathology; T-Lymphocytes, Helper-Inducer - immunology; T-Lymphocytes, Helper-Inducer - metabolism; T-Lymphocytes, Helper-Inducer - pathology; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; T-Lymphocytes, Regulatory - pathology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1002917

Activated T cells can acquire membrane molecules from APCs through a process termed trogocytosis. The functional consequence of this event has been a subject of debate. Focusing on transfer of peptide-MHC class II (MHC-II) complexes from APCs to CD4(+) T cells after activation, in this study we investigated the molecule acquisition potential of naturally occurring regulatory T cells (Tregs) and CD4(+) Th cells. We show that acquisition of membrane molecules from APCs is an inherent feature of CD4(+) T cell activation. Triggering of the TCR enables CD4(+) T cells to acquire their agonist ligands as well as other irrelevant membrane molecules from the interacting APCs or bystander cells in a contact-dependent manner. Notably, trogocytosis is a continuous process during cell cycle progression, and Th cells and Tregs have comparable capacity for trogocytosis both in vitro and in vivo. The captured peptide-MHC-II molecules, residing in sequestered foci on the host cell surface, endow the host cells with Ag-presenting capability. Presentation of acquired peptide-MHC-II ligands by Th cells or Tregs has either stimulatory or regulatory effect on naive CD4(+) T cells, respectively. Furthermore, Th cells with captured peptide-MHC-II molecules become effector cells that manifest better recall responses, and Tregs with captured ligands exhibit enhanced suppression activity. These findings implicate trogocytosis in different subsets of CD4(+) T cells as an intrinsic mechanism for the fine tuning of Ag-specific CD4(+) T cell response.