TY - JOUR
T1 - Short-term antigen presentation and single clonal burst limit the magnitude of the CD8+ T cell responses to malaria liver stages
AU - Hafalla, Julius C.R.
AU - Sano, Gen ichiro
AU - Carvalho, Luzia H.
AU - Morrot, Alexandre
AU - Zavala, Fidel
PY - 2002/9/3
Y1 - 2002/9/3
N2 - Malaria sporozoites induce swift activation of antigen-specific CD8+ T cells that inhibit the intracellular development of liverstage parasites. The length of time of functional in vivo antigen presentation, estimated by monitoring the activation of antigen-specific CD8+ T cells, is of short duration, with maximum T cell activation occurring within the first 8 h after immunization and lasting approximately 48 h. Although the magnitude of the CD8+ T cell response closely correlates with the number of parasites used for immunization, increasing the time of antigen presentation by daily immunizations does not enhance the magnitude of this response. Thus, once a primary clonal burst is established, the CD8+ T cell response becomes refractory or unresponsive to further antigenic stimulation. These findings strongly suggest that the most efficient strategy for the induction of primary CD8+ T cell responses is the delivery of a maximal amount of antigen in a single dose, thereby ensuring a clonal burst that involves the largest number of precursors to become memory cells.
AB - Malaria sporozoites induce swift activation of antigen-specific CD8+ T cells that inhibit the intracellular development of liverstage parasites. The length of time of functional in vivo antigen presentation, estimated by monitoring the activation of antigen-specific CD8+ T cells, is of short duration, with maximum T cell activation occurring within the first 8 h after immunization and lasting approximately 48 h. Although the magnitude of the CD8+ T cell response closely correlates with the number of parasites used for immunization, increasing the time of antigen presentation by daily immunizations does not enhance the magnitude of this response. Thus, once a primary clonal burst is established, the CD8+ T cell response becomes refractory or unresponsive to further antigenic stimulation. These findings strongly suggest that the most efficient strategy for the induction of primary CD8+ T cell responses is the delivery of a maximal amount of antigen in a single dose, thereby ensuring a clonal burst that involves the largest number of precursors to become memory cells.
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U2 - 10.1073/pnas.182189999
DO - 10.1073/pnas.182189999
M3 - Article
C2 - 12185251
AN - SCOPUS:0037015012
SN - 0027-8424
VL - 99
SP - 11819
EP - 11824
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 18
ER -