Recognition of antigens by T-cell receptors (TCRs) on the surface of T cells is central to the immune response, and may occur via a classical method of peptide antigen presentation by major histocompatibility complexes class I/II (MHC class-I/II); or non-classical lipid or vitamin metabolite antigen presentation by MHC class-I-like molecules cluster of differentiation molecule 1 (CD1) or MHC related protein 1 (MR1) respectively. Lipid antigen presentation by the CD1 family has more recently entered the spotlight with CD1s responsible for antigenic lipid presentation for TCR recognition. The CD1 family is divided in to 3 groups based on sequence identity and expression patterns; Group 1 (CD1a/b/c) and Group 2 (CD1d). All of the antigen presenting CD1 isoforms contain a unique binding grove which allows for antigen presentation and consequent T cell activation.
There has been a substantial volume of research conducted on foreign lipid presentation and recognition, by CD1b, due to its well-established role in Mycobacterium tuberculosis infection. Interestingly, we know little about the presentation of self-lipids by CD1b and consequent immune response, however, auto-reactive lipid-CD1b+ cell interactions play a crucial role in diseases including contact hypersensitivities, lupus, and psoriasis. CD1b is capable of presenting self-lipids, as lipids are critical in binding cleft stabilisation throughout the endosomal pathway until CD1b is loaded with antigenic lipids (1). However, the concept of self-lipids acting as antigenic targets is very new with crystal structures and functional data showing TCR interaction and consequent T cell activation by CD1b presenting self-lipids (2). To further understand the mechanisms behind the auto-reactivity of CD1b and CD1 restricted T-cells, presentation of self-lipids by CD1b has been established with members of the phospholipid, sphingolipid and ganglioside families. Protein production of CD1b was conducted, with representative phospholipids phosphatidylinositol (PI), and ganglioside GD3 (GD3) exogenously loaded into CD1b post-purification. The structures of CD1b-PI and CD1b-GD3 were determined via x-ray crystallography. In defining these structures, we are closer to elucidating the mechanism between the auto-reactive TCRs with lipid-bound CD1b+-APCs. This opens up an intriguing and relatively untapped area of research into the potential role of CD1b in self lipid presentation and consequent autoimmunity.