Cutting Edge: A Naturally Occurring Mutation in CD1e Impairs Lipid Antigen Presentation

Unité 725 Biology of Human Dendritic Cells, Institut National de la Santé et de la Recherche Médicale (INSERM), Strasbourg, France.
The Journal of Immunology (Impact Factor: 4.92). 04/2008; 180(6):3642-6. DOI: 10.4049/jimmunol.180.6.3642
Source: PubMed


The human CD1a-d proteins are plasma membrane molecules involved in the presentation of lipid Ags to T cells. In contrast, CD1e is an intracellular protein present in a soluble form in late endosomes or lysosomes and is essential for the processing of complex glycolipid Ags such as hexamannosylated phosphatidyl-myo-inositol, PIM(6). CD1e is formed by the association of beta(2)-microglobulin with an alpha-chain encoded by a polymorphic gene. We report here that one variant of CD1e with a proline at position 194, encoded by allele 4, does not assist PIM(6) presentation to CD1b-restricted specific T cells. The immunological incompetence of this CD1e variant is mainly due to inefficient assembly and poor transport of this molecule to late endosomal compartments. Although the allele 4 of CD1E is not frequent in the population, our findings suggest that homozygous individuals might display an altered immune response to complex glycolipid Ags.

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