Toxoplasma gondii and MHC-restricted antigen presentation: on degradation,transport and modulation

Resistance against Toxoplasma gondii, an obligate intracellular protozoan p arasite surrounded by a parasitophorous vacuolar membrane, is mediated by t he cellular arm of the immune system, namely CD8 + and CD4 + T cells. Thus, priming and activation of these cells by presentation of antigenic peptide s in the context of major histocompatibility complex class I and class II m olecules have to take place. This is despite the fact that the vacuolar mem brane avoids fusion with the endocytic compartment and acts like a molecula r sieve, restricting passive diffusion of larger molecules. This raises sev eral cell biological and immunological questions which will be discussed in this review in the context of our current knowledge about major histocompa tibility complex-restricted antigen presentation in other systems: (1) By w hich pathways are parasite-derived antigens presented to T cells? (2) Has t he parasite evolved mechanisms to interfere with major histocompatibility c omplex-restricted antigen presentation in order to avoid immune recognition ? (3) To what extent and by which mechanism is antigenic material, originat ing from the parasite, able to pass through the vacuolar membrane into the cytosol of the infected cell and is it then accessible to the antigen prese ntation machinery of the infected cell? (4) What are the actual antigen-pre senting cells which prime specific T cells in lymphoid organs? An understan ding of these mechanisms will not only provide new insights into the pathog enesis of Toxoplasma gondii and possibly other intravacuolar parasites, but will also improve vaccination strategies. (C) 2001 Australian Society for Parasitology Inc. Published by Elsevier Science Ltd. All rights reserved.