T lymphocytes are instrumental in the prevention of infections. With their antigen-specific T cell receptor (TCR), these cells recognize short peptides in the peptide-binding groove on MHC molecules of antigen-presenting cells. However, conventional T cells can also recognize non-peptide antigens including carbohydrates, phosphate groups, organic chemicals, and metal ions. The molecular basis of the interaction of TCR with these structures in the context of MHC has been partly solved. Organic chemicals and carbohydrates are recognized when bound to MHC-associated peptides, whereas metal ions are recognized due to their ability to form non-covalent coordination bonds with MHC molecules, bound peptides, and TCR. Peptide-independent metal ion recognition has also been described.