TY - JOUR
T1 - Preferential escape of subdominant CD8+ T cells during negative selection results in an altered antiviral T cell hierarchy
AU - Slifka, Mark K.
AU - Blattman, Joseph N.
AU - Sourdive, David J.D.
AU - Liu, Fei
AU - Huffman, Donald L.
AU - Wolfe, Tom
AU - Hughes, Anna
AU - Oldstone, Michael B.A.
AU - Ahmed, Rafi
AU - Von Herrath, Matthias G.
PY - 2003/2/1
Y1 - 2003/2/1
N2 - Negative selection is designed to purge the immune system of high-avidity, self-reactive T cells and thereby protect the host from overt autoimmunity. In this in vivo viral infection model, we show that there is a previously unappreciated dichotomy involved in negative selection in which high-avidity CD8+ T cells specific for a dominant epitope are eliminated, whereas T cells specific for a subdominant epitope on the same protein preferentially escape deletion. Although this resulted in significant skewing of immunodominance and a substantial depletion of the most promiscuous T cells, thymic and/or peripheral deletion of high-avidity CD8+ T cells was not accompanied by any major change in the TCR Vβ gene family usage of an absolute deletion of a single preferred complementarity-determining region 3 length polymorphism. This suggests that negative selection allows high-avidity CD8+ T cells specific for subdominant or cryptic epitopes to persist while effectively deleting high-avidity T cells specific for dominant epitopes. By allowing the escape of subdominant T cells, this process still preserves a relatively broad peripheral TCR repertoire that can actively participate in antiviral and/or autoreactive immune responses.
AB - Negative selection is designed to purge the immune system of high-avidity, self-reactive T cells and thereby protect the host from overt autoimmunity. In this in vivo viral infection model, we show that there is a previously unappreciated dichotomy involved in negative selection in which high-avidity CD8+ T cells specific for a dominant epitope are eliminated, whereas T cells specific for a subdominant epitope on the same protein preferentially escape deletion. Although this resulted in significant skewing of immunodominance and a substantial depletion of the most promiscuous T cells, thymic and/or peripheral deletion of high-avidity CD8+ T cells was not accompanied by any major change in the TCR Vβ gene family usage of an absolute deletion of a single preferred complementarity-determining region 3 length polymorphism. This suggests that negative selection allows high-avidity CD8+ T cells specific for subdominant or cryptic epitopes to persist while effectively deleting high-avidity T cells specific for dominant epitopes. By allowing the escape of subdominant T cells, this process still preserves a relatively broad peripheral TCR repertoire that can actively participate in antiviral and/or autoreactive immune responses.
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U2 - 10.4049/jimmunol.170.3.1231
DO - 10.4049/jimmunol.170.3.1231
M3 - Article
C2 - 12538681
AN - SCOPUS:0037310510
SN - 0022-1767
VL - 170
SP - 1231
EP - 1239
JO - Journal of Immunology
JF - Journal of Immunology
IS - 3
ER -