Most foreign antigens are "processed" by APC into a form in which they can bind MHC molecules and be recognised by the TCR. Functional and immuno-gold labelling studies have been used to determine the putative sites of MHC-Ag interaction following uptake of Leishmania donovani into a phagolysosome. During infection with this parasite in vivo, upregulation of class II occurs. Based on studies using scid mice, NK cells appear to contribute little to this process. During chronic infection, however, APC function is diminished in spite of high class II levels. We propose that a lack of coordinate costimulator expression may lead to subsequent loss of T cell function late in infection, by a mechanism involving the induction of T cell unresponsiveness.