LIGHT (a cellular ligand for herpes virus entry mediator and lymphotoxin receptor)-mediated thymocyte deletion is dependent on the interaction between TCR and MHC/self-peptide.
Negative selection serves as a major mechanism to maintain self-tolerance. We previously reported that LIGHT (a cellular ligand for herpes virus entry mediator and lymphotoxin receptor), a TNF family member, plays an important role in thymocyte development via promoting apoptosis of double-positive thymocytes. Here, we demonstrated that LIGHT-mediated deletion of thymocyte requires the strong interaction of TCR with MHC/self-peptide. Transgenic mice overexpressing LIGHT in thymocytes were bred with a transgenic mouse line expressing a TCR recognizing the H-Y male Ag in the context of H-2b class I MHC molecules. In male H-Y/LIGHT double-transgenic mice, more efficient negative selection of H-Y T cells occurred, and total thymocyte number was further reduced compared with H-Y/negative littermates. In contrast, the presence of LIGHT transgene had no evident impact on the thymocyte development of female H-Y/LIGHT double-transgenic mice. Taken together, LIGHT plays a role in negative selection of thymocytes via inducing the apoptosis of thymocytes bearing high affinity TCR during negative selection.
Wang
Jing
J
Department of Pathology and Committee on Immunology, University of Chicago, Chicago, IL 60637, USA.
Fu
Yang-Xin
YX
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D001324:Autoantigens / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D017637:Clonal Deletion / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000378:metabolism; D005260:Female; D006182:H-Y Antigen / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D008024:Ligands; D053259:Lymphotoxin beta Receptor; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism / Q000502:physiology; D053240:Receptors, Tumor Necrosis Factor, Member 14; D011991:Receptors, Virus / Q000378:metabolism; D012727:Sex Characteristics; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D001324:Autoantigens; D018984:Epitopes, T-Lymphocyte; D006182:H-Y Antigen; D008024:Ligands; C505699:Ltbr protein, mouse; D053259:Lymphotoxin beta Receptor; D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; D018124:Receptors, Tumor Necrosis Factor; D053240:Receptors, Tumor Necrosis Factor, Member 14; D011991:Receptors, Virus; C506029:Tnfrsf14 protein, mouse; C505915:Tnfsf14 protein, mouse; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D014409:Tumor Necrosis Factor-alpha