Genetic studies have shown the association of Parkinson's disease with alleles of the major histocompatibility complex(1-3). Here we show that a defined set of peptides that are derived from a-synuclein, a protein aggregated in Parkinson's disease(4), act as antigenic epitopes displayed by these alleles and drive helper and cytotoxic T cell responses in patients with Parkinson's disease. These responses may explain the association of Parkinson's disease with specific major histocompatibility complex alleles.