Myeloid differentiation factor 88 is required for cross-priming in vivo.

Abstract

We describe a role for myeloid differentiation factor 88 (MyD88) in the induction of functional CTLs in vivo, in response to exogenously administered Ag, using a heat shock fusion protein, hsp65-P1, as a model Ag. CD8 T cells transferred into MyD88-deficient animals produce normal numbers of CD8 effector cells that have normal activation marker profiles after immunization with hsp65-P1. However, these CD8 T cells produced significantly less IFN-gamma and showed reduced killing activity. This reduction in activation of functional CTLs appears to be unrelated to Toll-like receptor 4 function, because in vitro hsp65-P1-experienced Toll-like receptor 4-deficient dendritic cells (DCs), but not MyD88-deficient DCs, activated CD8 T cells to a similar extent to wild-type DCs. We identify a cross-presentation defect in MyD88-deficient DCs that, when treated with hsp65-P1 fusion protein, results in surface display of fewer SIYRYYGL/class I MHC complexes. Thus, MyD88 plays a role in the developmental maturation of DCs that allows them to prime CD8 T cells through cross-presentation.