In vivo expression of a TCR antagonist: T cells escape central tolerance but are antagonized in the periphery.
Transgenic 3.L2 T cells are stimulated by Hb(64-76)/I-Ek and are positively selected on I-Ek plus self-peptides. To this pool of self-peptides we have added a single, well-defined 3.L2 TCR antagonist (A72) in vivo. We find that mice expressing both the 3.L2 TCR and A72 have a minimal loss of T cells expressing the clonotypic TCR in the thymus and spleen. Importantly, the proliferative response of 3.L2 x A72 splenocytes is significantly reduced compared with splenocytes from 3.L2 mice. This reduced response can be attributed to peripheral antagonism. Thus we have identified a new class of self-ligands whose predominant effect is constitutive peripheral antagonism rather than negative selection. The net effect of these ligands is to avoid potential self-reactivity while maintaining as large a repertoire as possible.
Williams
C B
CB
Department of Pediatrics, Center for Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Vidal
K
K
Donermeyer
D
D
Peterson
D A
DA
White
J M
JM
Allen
P M
PM
D000818:Animals; D000938:Antigen-Presenting Cells / Q000378:metabolism; D002645:Chickens; D002999:Clone Cells; D006454:Hemoglobins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007108:Immune Tolerance / Q000187:drug effects; D008024:Ligands; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D051379:Mice; D008806:Mice, Inbred AKR; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009113:Muramidase / Q000235:genetics / Q000276:immunology; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D019076:Transgenes / Q000276:immunology
D006454:Hemoglobins; D000949:Histocompatibility Antigens Class II; D008024:Ligands; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins; C079201:hemoglobin (64-76); C066759:hen egg lysozyme peptide (46-61); D009113:Muramidase