T-CELL RESPONSE TO HIV IN NATURAL INFECTION - OPTIMIZED CULTURE CONDITIONS FOR DETECTING RESPONSES TO GAG PEPTIDES

The proliferative responses to four gag peptides were examined in 24 H IV-seropositive patients whose CD4 counts ranged between 500 and 1400 cells/mm(3). To overcome some of the limitations imposed by HIV infect ion on the T-cell proliferative assay, recombinant interleukin 2 (rIL- 2) was added to the cultures, and the culture time of the cells was in creased from the standard 6 to 8 or 10 days. Four of 24 patients respo nded to one or more core peptides, aa180-194, 208-217, 267-286, and 28 7-306 by the standard 6-day culture: this increased to 13 of 24 using the optimized culture approach. The greatest number and magnitude of r esponses occurred after cells were in culture for 8 days. Eight patien ts responded to gag 180-194, which has not been identified previously as a TH epitope in humans but has considerable homology with a TH epit ope recognized by cloned T cells from macaques immunized with simian i mmunodeficiency virus (SIV). We have identified four T-cell epitopes o n the HIV core protein p24, using synthetic peptides as immunogens. Th ree of the peptides would not have been considered immunogenic had the standard assay system been used to detect T-cell responsiveness, We h ave also shown that a region of the core protein encompassed by aa180- 194 is recognized by TH cells in humans.