Our immune system constantly samples peptides found inside the body as a means to detect foreign pathogens, infected cells, and tumorous cells. T cells, which carry out the critical task of distinguishing self from nonself peptides, can only survey peptides that are presented by the major histocompatibility complex protein. We investigated how the secondary structure of a peptide, namely, the polyproline II helix content, influences major histocompatibility complex binding. We synthesized 12 analogues of the wheat gluten derived α-I-gliadin peptide and tested their binding to the celiac disease associated HLA-DQ2 protein. Our analogue library represents a broad spectrum of polyproline II propensities, ranging from random coil structure to high polyproline II helix content. Overall, there was no noticeable correlation between the peptide polyproline II helix content and HLA-DQ2 binding. One analogue peptide, which has low polyproline II helix content, showed a 4.5-fold superior binding compared to native α-I-gliadin.