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Extra resources for Annual Review of Immunology Volume 21 2003
Some attempts have been made to measure antigen presentation in vivo (181), but we remain constrained by the limitations of available methods. The antigenicity of secreted versus nonsecreted (somatic) proteins has been investigated. Hess and colleagues studied immunity induced by Salmonella strains expressing Listeria antigens in secreted or somatic forms. They showed that secreted antigens were superior to somatic antigens at inducing protective T cell responses (182). Priming of CD8 T cells by Salmonella secreting a Listeria protein is TAP dependent, indicating that, despite initial vacuolar localization, secreted antigens access the APC cytosol (183).
On the other hand, another Listeria protein, ActA, has enhanced stability in the cytosol because it contains a stabilizing amino acid at the amino-terminus (179). Interestingly, LLO, the membranolytic virulence factor that is potentially highly toxic to the host cell, is rapidly degraded in a proteasome-dependent fashion (177) because it contains a PEST-like sequence (180). Investigation of bacterial antigen presentation is much more difficult in vivo than in vitro. SGM LaTeX2e(2002/01/18) Annu.
In C57BL/6 mice, the three dominant peptides are bound by H-2Db with high affinity and with long half-lives, but they are present at different densities on the cell surface, with gp33 > np396 > gp276 (22). Their abundance correlates with the magnitude of CTL responses to these epitopes following LCMV infection. However, the magnitude of a particular response does not necessarily correlate with its protective antiviral capacity because subsequent adoptive transfer experiments showed that when equal numbers of CTLs specific for the gp33, np396, or gp276 peptides were injected into infected mice, np396-specific CTLs conferred optimum protection, followed by gp276- and finally gp33-specific T cells.