The aim of the present study was to analyze the interactions between HLA-B27-binding β-octa- and β-nona-peptides, which may contain up to three α amino-acid residues, and the cognate T-cell receptor specifically targeting the dominant HIV-derived HLA-B27-restricted viral epitope KK10 (KRWIILGLNK). To this end, the IFNγ production by the T cells was quantified by ELISPOT assays in the presence or absence of several β-peptidic compounds, designed to bind to B27, and to study the interference with TCR recognition. In the presence of the B27-KK10 natural α-peptide IFNγ secretion by the CD8+ T-cell line was observed at millimolar concentrations. In contrast, a dose-dependent reduction of IFNγ secretion was found, following co-incubation with HLA-B27 specific β-peptides.Suppression of T cell activity was demonstrated starting at 10-fold higher concentrations of the β-peptidic additives as compared to the α-peptide. Certain α- and β-peptides, which did not interfere with the IFNγ response of HLA-B27-restricted CD8+ T cells, were used as negative controls.