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Secreted and surface-exposed antigens of intracellular pathogens are thought to provide target structures for detection by the host immune system. The major secreted product of intracellularLeishmania mexicana amastigotes, a proteophosphoglycan (aPPG), is known to contribute to the establishment of the parasitophorous vacuole and is able to activate complement. aPPG belongs to a novel class of serine- and threonine-richLeishmania proteins that are extensively modified by phosphodiester-linked phosphooligosaccharides and terminal mannooligosaccharides. Here we show that mice chronically infected withL. mexicana generally do not produce antibodies or Th cells specific for aPPG. Similarly, antibody titers are very low in mice vaccinated with aPPG, and specific CD4+ T cells are undetectable. Comparative analyses of otherLeishmania glycoconjugates indicate thatL. mexicana -specific carbohydrate structures are poorly immunogenic in mice and that the proteophosphoglycan aPPG behaved immunologically like a carbohydrate. The latter observation is explained by the lack of induction of aPPG-specific CD4+ T cells. In contrast, recombinant aPPG peptides stimulate CD4+ T-cell responses and high titers of specific antibodies are found in the sera of mice vaccinated with these peptides. Native aPPG is highly resistant to proteinases and apparently cannot be degraded by macrophages. It is concluded that conventional CD4+ T cells against the polypeptide backbone of aPPG are not induced because the molecule resists antigen processing due to its extensive and complex carbohydrate modification. The complex glycan chains of aPPG, which exhibit important biological functions for the parasite, may therefore also have evolved to evade detection by the immune system of the host organism.

infection and immunity

Proteophosphoglycan, a Major Secreted Product of Intracellular<i>Leishmania mexicana</i>Amastigotes, Is a Poor B-Cell Antigen and Does Not Elicit a Specific Conventional CD4<sup>+</sup>T-Cell Response

Proteophosphoglycan, a Major Secreted Product of IntracellularLeishmania mexicanaAmastigotes, Is a Poor B-Cell Antigen and Does Not Elicit a Specific Conventional CD4+T-Cell Response

Proteophosphoglycan, a Major Secreted Product of IntracellularLeishmania mexicanaAmastigotes, Is a Poor B-Cell Antigen and Does Not Elicit a Specific Conventional CD4⁺T-Cell Response