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(1995) Identification of conserved antigenic components for a cytotoxic T lymphocyte- inducing vaccine against malaria. Lancet 345, 1003–1007 TRENDS in Parasitology Vol.17 No.5 May 2001 http://parasites.trends.com 1471-4922/01/$ – see front matter © 2001 Elsevier Science Ltd. All rights reserved. PII: S1471-4922(01)01895-5 223 Opinion Leishmania parasites assemble an abundance of distinctive glycoconjugates that are expressed on their surface or secreted 1–3 (Fig. 1). Leishmania produce a characteristic family of glycoconjugates containing phosphoglycan (PG) that includes membrane-bound lipophosphoglycan (LPG) and proteophosphoglycan (PPG), as well as secreted PG, PPG and acid phosphatase (sAP). In addition, the surface of Leishmania contains an array of molecules attached to glycosylphosphatidylinositol (GPI) anchors (Fig. 1). These include free entities such as glycosylinositolphospholipids (GIPLs), LPG itself and proteins including the promastigote surface protease (also known as leishmanolysin, PSP or gp63). The abundance, location and uniqueness of these Leishmania structures have led to the suggestion that these glycoconjugates, particularly LPG, have one or more important functions for the parasite throughout its life cycle 2,4,5 . These include the procyclic and metacyclic promastigotes carried by the sand fly vector, and the amastigote stage, which resides within the phagolysosome of macrophages (Fig. 2). Most of the roles proposed for the glycoconjugates have been deduced using purified molecules and examining their effects on mouse macrophage function and interactions with the sand fly vector. From these in vitro experiments, there is substantial evidence that LPG is required for survival during the initial stage of establishment in the macrophage, when the parasite is most vulnerable. For example, LPG (or purified portions thereof ) has been shown to bind macrophages and to inhibit macrophage signal transduction and cytokine production 5,6 . However, the distribution of PG units and GPI anchors across a large number of different molecules (Fig. 1) raises questions about the correct assignment of functions for the individual glycoconjugates. Assays of LPG function using purified LPG might mimic effects that normally arise through other PGs or GPI-anchored molecules. This problem is compounded by the fact that LPG (or portions thereof ) is often tested outside the biological milieu, at concentrations that might exceed that attained during parasite invasion. The use of parasite mutants provides an opportunity to test the role of LPG in a biologically relevant setting. Examples of these include the Is lipophosphoglycan a virulence factor? A surprising diversity between Leishmania species Salvatore J. Turco, Gerald F. Späth and Stephen M. Beverley Lipophosphoglycan is a prominent member of the phosphoglycan-containing surface glycoconjugates of Leishmania. Genetic tests enable confirmation of its role in parasite virulence and permit discrimination between the roles of lipophosphoglycan and related glycoconjugates. When two different lipophosphoglycan biosynthetic genes from Leishmania major were knocked out, there was a clear loss of virulence in several steps of the infectious cycle but,with Leishmania mexicana, no effect on virulence was found. This points to an unexpected diversity in the reliance of Leishmania species on virulence factors, a finding underscored by recent studies showing great diversity in the host response to Leishmania species.