HIV-1-specific T cell responses correlate with control of infection and disease, thus encouraging a full understanding of the peptides and antigen-processing mechanisms that govern T cell activation. We have previously demonstrated that CD4(+) T cell epitopes cluster nonrandomly within envelope protein "hotspot" regions. The current study was initiated to determine whether envelope-specific CD8(+) T cells might share epitope "hotspots" with the CD4(+) T cell population. Identification of CD8(+) T cell determinants by ELISPOT assays with peripheral blood mononuclear cells from four HIV-1-infected individuals, in conjunction with a survey of determinants in the Los Alamos database, revealed similarities among "hotspot" positions for CD4(+) and CD8T(+) cells within mice and humans. These results emphasized the important influence that envelope peptide position may have on antigen processing, and the consequent impact such processing may have on HIV-1-specific CD4(+) and CD8(+) T-cell activities.