The impact of self-tolerance on the polyclonal CD8+ T cell repertoire.
TCRs possess considerable cross-reactivity toward structurally related Ags. Because the signaling threshold for negative selection is lower than that required for activation of mature T cells, the question arises as to which extent thymic deletion of self-specific T cells affects T cell responsiveness toward foreign peptides. In this study we show, in three different mouse models systems, that the polyclonal CD8(+) T cell repertoire has a marked ability to react against the majority of Ags related to self despite self-tolerance, even in cases where self and foreign differ only marginally at a single TCR-contact residue. Thus, while individual T cells are markedly cross-reactive, the ability to distinguish between closely related Ags is introduced at the polyclonal T cell level.
Kessels
Helmut W H G
HW
Department of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
de Visser
Karin E
KE
Tirion
Felicia H
FH
Coccoris
Miriam
M
Kruisbeek
Ada M
AM
Schumacher
Ton N M
TN
D019943:Amino Acid Substitution / Q000276:immunology; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D017637:Clonal Deletion / Q000235:genetics / Q000276:immunology; D002999:Clone Cells; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D005260:Female; D006182:H-Y Antigen / Q000276:immunology; D016056:Immunodominant Epitopes / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology; D008024:Ligands; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000276:immunology; D011485:Protein Binding / Q000276:immunology; D017634:Self Tolerance / Q000235:genetics / Q000276:immunology*; D014758:Viral Core Proteins / Q000276:immunology
D000952:Antigens, Polyomavirus Transforming; D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D006182:H-Y Antigen; D016056:Immunodominant Epitopes; D008024:Ligands; D010446:Peptide Fragments; D014758:Viral Core Proteins; C102366:nucleoprotein (366-374), influenza virus