Human CD1-restricted T cell recognition of lipids from pollens

Abstract

Plant pollens are an important source of environmental antigens that stimulate allergic responses. In addition to acting as vehicles for foreign protein antigens, they contain lipids that incorporate saturated and unsaturated fatty acids, which are necessary in the reproduction of higher plants. The CD1 family of nonpolymorphic major histocompatibility complex–related molecules is highly conserved in mammals, and has been shown to present microbial and self lipids to T cells. Here, we provide evidence that pollen lipids may be recognized as antigens by human T cells through a CD1-dependent pathway. Among phospholipids extracted from cypress grains, phosphatidyl-choline and phosphatidyl-ethanolamine were able to stimulate the proliferation of T cells from cypress-sensitive subjects. Recognition of phospholipids involved multiple cell types, mostly CD4+ T cell receptor for antigen (TCR)αβ+, some CD4−CD8− TCRγδ+, but rarely Vα24i + natural killer–T cells, and required CD1a+ and CD1d+ antigen presenting cell. The responding T cells secreted both interleukin (IL)-4 and interferon-γ, in some cases IL-10 and transforming growth factor-β, and could provide help for immunoglobulin E (IgE) production. Responses to pollen phospholipids were maximally evident in blood samples obtained from allergic subjects during pollinating season, uniformly absent in Mycobacterium tuberculosis–exposed health care workers, but occasionally seen in nonallergic subjects. Finally, allergic, but not normal subjects, displayed circulating specific IgE and cutaneous weal and flare reactions to phospholipids.

The cellular and biochemical rules of lipid antigen presentation

“…First, are T cells tolerant to self-lipids loaded on CD1 molecules in the ER? This is not the case in patients with pollen allergy, which have circulating PC-specific T cells [21]. A second issue is how PC moves from the ER membrane into nascent CD1b and CD1d molecules.…”

“…For example, phosphatidylcholine (PC) and phosphatidylethanolamine extracted from cypress grains induce CD1 group 1 and 2-restricted immune responses [21]. The frequency of these T cells increases in patients with pollen allergy during pollination and decreases in winter, suggesting an environment-related stimulation.…”

γδ-T cells: an unpolished sword in human anti-infection immunity

“…These phosphoantigens are usually natural metabolites of isoprenoid biosynthesis in host cells, which include IPP, (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate, dimethylallyl pyrophosphate (DMAPP) 53,54 and bromohydrin pyrophosphate. 55 These phosphoantigens can be presented by T cells, monocytes and various antigen-presenting cells (APCs), such as DCs and B cells, 56,57 through expression of CD1d 58,59 and as-yet unknown non-MHC molecules on host cells. 60 The clinical applications of phosphoantigens in cd-T cell-based therapy will be discussed in a later part of this review.…”

Diversity of γδ T-cell antigens

“…33 The related group 2 CD1 molecule, CD1d, appears to be recognized by both human and murine cd T cells. [34][35][36][37] The same molecule has been studied in detail as a ligand for classical natural killer T cells, 38 also both in mice and humans. With natural killer T cells, CD1d serves as presenter of certain lipids, and there is some evidence that cd T cells in humans and mice also recognize a CD1d/lipid complex.…”

“…Thus, cloned human cd T cells responded to phosphatidyl ethanol amine (PE) in a manner dependent on CD1d, which suggested CD1d-restricted recognition of this phospholipid. 34,35,39 The phospholipid cardiolipin (CL) binds to CD1d and murine cd T cells responded both in vivo and in vitro to CL dependent on the presence of CD1d, suggesting that this phospholipid is also presented by CD1d, and is thus recognized by the cd T cells. 36 Finally, CD1d appears to present sulfatide, an abundant myelin glycosphingolipid, to human cd T cells expressing Vd1.…”