MAJOR HISTOCOMPATIBILITY COMPLEX CLASS I-RESTRICTED CROSS-PRESENTATION IS BIASED TOWARDS HIGH-DOSE ANTIGENS AND THOSE RELEASED DURING CELLULAR DESTRUCTION
C. Kurts et al., MAJOR HISTOCOMPATIBILITY COMPLEX CLASS I-RESTRICTED CROSS-PRESENTATION IS BIASED TOWARDS HIGH-DOSE ANTIGENS AND THOSE RELEASED DURING CELLULAR DESTRUCTION, The Journal of experimental medicine, 188(2), 1998, pp. 409-414
Naive T cells recirculate mainly within the secondary lymphoid compart
ment, but once activated they can enter peripheral tissues and perform
effector functions. To activate naive T cells, foreign antigens must
traffic from the site of infection to the draining lymph nodes, where
they can be presented by professional antigen presenting cells. For ma
jor histocompatibility complex class I-restricted presentation to CD8(
+) T cells, this can occur via the cross-presentation pathway. Here, w
e investigated the conditions allowing antigen access to this pathway.
We show that the level of antigen expressed by peripheral tissues mus
t be relatively high to facilitate cross-presentation to naive CD8(+)
T cells. Below this level, peripheral antigens did not stimulate by cr
oss-presentation and were ignored by naive CD8(+) T cells, although th
ey could sensitize tissue cells for destruction by activated cytotoxic
T lymphocytes (CTLs). Interestingly, CTL-mediated tissue destruction
facilitated cross-presentation of low dose antigens for activation of
naive CD8(+) T cells. This represents the first in vivo evidence that
cellular destruction can enhance access of exogenous antigens to the c
ross-presentation pathway. These data indicate that the cross-presenta
tion pathway focuses on high dose antigens and those released during t
issue destruction.