Presentation of acquired peptide-MHC class II ligands by CD4+ regulatory T cells or helper cells differentially regulates antigen-specific CD4+ T cell response.
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.
Cancer Immunotherapy Program, Medical College of Georgia Cancer Center, Medical College of Georgia, Augusta, GA 30912, USA. GZHOU@mcg.edu
Gang
G
Zhou
Zhi-Chun
ZC
Ding
Jie
J
Fu
Hyam I
HI
Levitsky
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015704:CD4 Antigens / Q000096:biosynthesis / Q000502:physiology*; D045744:Cell Line, Tumor; D002645:Chickens; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism*; D007156:Immunologic Memory; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010455:Peptides / Q000276:immunology / Q000378:metabolism*; D025941:Protein Interaction Mapping; D012513:Sarcoma, Experimental / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
D015704:CD4 Antigens; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; D008024:Ligands; D010455:Peptides