Air pollution is a major global health threat contributing to millions of annual deaths. Air pollutants as non-heritable factors are now recognized as triggers for multiple human inflammatory disorders involving T cells. We postulate that lipid antigen presentation for T cell activation is susceptible to lipophilic air pollutants, such as polycyclic aromatic hydrocarbons. To test this hypothesis, we determined whether the common polycyclic aromatic hydrocarbons, benzo[a]pyrene and diesel exhaust particles, impact on the activation of lipid-specific T cells. Our results demonstrated that the expression of CD1a and CD1d proteins, and the activation of CD1a- and CD1d-restricted T cells were sensitively inhibited by benzo[a]pyrene even at the low concentrations detectable in exposed human populations. Similarly, diesel exhaust particles showed a marginal inhibitory effect. Using transcriptomic profiling, we discovered that the gene expression for regulating the endocytic function, lipid metabolism, and the production of cytokines and chemokines was perturbed by benzo[a]pyrene. Imaging flow cytometry also showed that CD1a and CD1d proteins were retained in early and late endosomal compartments, respectively, supporting an impaired endocytic lipid antigen presentation for T cell activation upon benzo[a]pyrene exposure. This work conceptually demonstrates that lipid antigen presentation for T cell activation is inhibited by lipophilic pollutants through profound interference with gene expression and endocytic function, likely further disrupting regulatory cytokine secretion and ultimately exacerbating inflammatory diseases.