An affinity/avidity model of peripheral T cell regulation.
We show in these studies that Qa-1-dependent CD8+ T cells are involved in the establishment and maintenance of peripheral self tolerance as well as facilitating affinity maturation of CD4+ T cells responding to foreign antigen. We provide experimental evidence that the strategy used by the Qa-1-dependent CD8+ T cells to accomplish both these tasks in vivo is to selectively downregulate T cell clones that respond to both self and foreign antigens with intermediate, not high or low, affinity/avidity. Thus, the immune system evolved to regulate peripheral immunity using a unified mechanism that efficiently and effectively permits the system to safeguard peripheral self tolerance yet promote the capacity to deal with foreign invaders.
Jiang
Hong
H
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA. hj4@columbia.edu
Wu
Yilun
Y
Liang
Bitao
B
Zheng
Zongyu
Z
Tang
Guomei
G
Kanellopoulos
Jean
J
Soloski
Mark
M
Winchester
Robert
R
Goldstein
Itamar
I
Chess
Leonard
L
D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000276:immunology; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D017634:Self Tolerance / Q000235:genetics / Q000276:immunology*
D001324:Autoantigens; D015395:Histocompatibility Antigens Class I; C032907:Q surface antigens