CD1c mediates B cell presentation of self and foreign isoprenoid glycolipids to T cells

Moody, DB; Muhlacker, W; Young, D; Costello, C; Grant, E; Brenner, MB; Besra, GS; Porcelli, SA

doi:10.1002/art.1780422105

CD1c mediates B cell presentation of self and foreign isoprenoid glycolipids to T cells

Lookup NU author(s): Professor Del Besra

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Abstract

The CDllamilyol proteins (COla, CDlb, CDlc, COld) mediates T cell recognition of lipid antigons. The human COle protein is expressed on rosting Bcells and is known to mediate both autoreactive and antigen-dependent T cell responses. Here we report the identification of the first known COle presented lipid antigen to be a family of isoprenoid phosphoglycolipids. The natural anligen recognized by human lX~ T cell line was purified from Mycobacterium avium using silica chromatography and determined by gas chromatography and mass spectroscopy to be a novel mannosyl phosphodolichol (MPDl) containing a fully saturated isoprenoid lipid. Recognition of MPO absolutely rSQuiredCOle expression as determined by cytolysis of B Iymphoblastoid target cells. T cells that proliferate in vitro to MOP were detected in 6 of 6 donors studied. suggesting that MOP reactivity is common in humans. long chain isoprenoidS function to transfer carbohydrates in basic biosynthetic processes such as N-linked glycosylation and are present in all living cells,but vary In their fine structure between different genera. Therefore, COle-reStricted T cell lines were tested for proliferation to semi-synthetic isoprenoid glycollpids characteristic of various species. Surprisingly, all T cell lines tested responded to the MOPs characteristic of eukaryotes, but not the analogous mannosyl phosphopolyprenols that are typical of prokaryotes. In fact, one human T cell line proliferated in response to MOP synthesized from human hepatic dolichol, defining the first lipid autoantigen for human T cells. These results indicate that B cells can present a family of structurally related sell and foreign lipids for T cell recognition, providing a potential molecular mechanism for generating T cell dependent immunoglobin responses against sell glycolipids.