In this study, we show that the
glucose-regulated protein 94 (
GRP94) from Leishmania infantum is a major target for humoral immune response during both visceral (VL) and
mucocutaneous leishmaniasis (MCL). Also, the time-course of appearance of anti-GRP94
antibodies along the
infection was analysed in hamsters (Mesocricetus auratus) experimentally infected with L. infantum. Remarkably, the reactivity against the Leishmania
GRP94 was observed very soon after challenge, at the time of appearance of a humoral response against Leishmania total
proteins, and long before that the animals develop clinical symptoms of disease. Therefore, at least for golden hamsters, the reactivity against Leishmania
GRP94 is an early marker of
infection. Using a collection of synthetic
peptides covering the complete sequence of the L. infantum
GRP94, we have determined the main linear
antigenic determinants recognised by sera from humans, dogs, and hamsters suffering from VL. Four synthetic
peptides, located in highly divergent regions of the
protein, were found to be immunodominants and recognised by VL sera of these three different origins. We discuss that the prominent antigenicity of Leishmania
GRP94 may be related to recent findings involving
GRP94, and other
heat shock proteins, in relevant immune functions such as tumour immunogenicity and antigen presentation.