T cell mediated hypersensitivity to metal cations is common in humans. How the T cell antigen receptor (TCR) recognizes these cations bound to a major histocompatibility complex (MHC) protein associated with a self-peptide is unknown. Individuals carrying the class II MHC (MHCII) allele, HLA-DP2, are at risk for chronic beryllium disease (CBD), a CD4 T cell mediated, debilitating lung inflammatory condition caused by inhaled beryllium. Here we show that, unexpectedly, a Be2+ cation becomes buried in an HLA-DP2/peptide complex where it is coordinated by both MHC and peptide acidic amino acids. The TCR does not react with the cation itself; rather, it indirectly recognizes changes on the MHC/peptide surface induced by the firmly bound Be2+. Thus, Be2+ binding is a unique form of MHC-peptide modification that creates a new antigen from pre-existing self-components without directly interacting with the T cell, placing CBD on the border between allergy and autoimmunity.