Central to both innate and adaptive immunity is the mediation of T-cell recognition of antigen presenting molecules presenting antigens by T-cell receptors (TCR). CD1 molecules are Major Histocompatibility Complex class I like molecules involved in presentation of foreign and self-lipid antigens. CD1b, a member of group 1 CD1 molecules along with CD1a and CD1c, exhibits the largest hydrophobic antigen binding cleft, capable of presenting foreign and self-lipids with long carbon tails. While the first molecular mechanisms regulating T-cell reactivity towards microbial lipids presented by CD1b has recently been portrayed in the context of Mycobacterium tuberculosis infection, the structural mechanisms surrounding T-cell autoreactivity towards self-lipid antigens are unknown. Following up from decades-long interest in phospholipid-specific antibodies, recent work shows that human T-cells, including the named clones PG90, PG10, HJ1, recognize CD1b presenting self-phospholipids, circulate in human blood and mediate autoimmune skin disease in a human TCR transgenic model. Our elution studies demonstrate that while CD1b presents common membrane phospholipids, alpha/beta TCR reactivity is specifically skewed towards the rare self-phospholipid, phosphatidylglycerol (PG). Cellular levels of PG are low in absolute terms, highly regulated, and are predominantly localised within mitochondria under normal physiological conditions. Biophysical analysis of these TCRs by surface plasmon resonance reveals a high sub-micromolar affinity interaction for CD1b-PG. Structural characterisation of the PG90 TCR-CD1b-PG complex provides the first insights into the molecular mechanisms for rare phospholipid discrimination.  The crystal structure demonstrates a dramatic induced fit model over the PG polar headgroup, primarily driven by rearrangement of the TCR CDR3 loops. Moulding of the TCR CDR3 loops forms a small, electrostatically positive pocket, denoted as a “cationic cup”, which selects against ubiquitous phospholipids through electrostatic or stearic hindrance. This provides insight into mechanisms of TCR autoreactivity geared towards rare self-phospholipids, thus improving our understanding towards detrimental T-cell autoreactivity against self-lipid antigens.