Identification of chlamydia trachomatis antigens recognized by t cells from highly exposedwomen who limit or resist genital tract infection

Abstract

Background. Natural infection induces partial immunity to Chlamydia trachomatis. Identification of chlamydial antigens that induce interferon ? (IFN-) secretion by T cells from immune women could advance vaccine development. Methods. IFN-? production by CD4+ and CD8+ peripheral blood T cells from 58 high-risk women was measured after coculture with antigen-presenting cells preincubated with recombinant Escherichia coli expressing a panel of 275 chlamydial antigens. Quantile median regression analysis was used to compare frequencies of IFN-? responses in women with only cervical infection to those in women with endometrial infection and frequencies in women who remained uninfected for over 1 year to those in women who developed incident infection. Statistical methods were then used to identify proteins associated with protection. Results. A higher median frequency of CD8+ T-cell responses was detected in women with lower genital tract chlamydial infection, compared with those with upper genital tract chlamydial infection (13.8% vs 9.5%; P = .04), but the CD4+ T-cell response frequencies were not different. Women who remained uninfected displayed a greater frequency of positive CD4+ T-cell responses (29% vs 18%; P < .0001), compared with women who had incident infection, while the frequencies of CD8+ T-cell responses did not differ. A subset of proteins involved in central metabolism, type III secretion, and protein synthesis were associated with protection. Conclusions. Investigations in naturally exposed women reveal protective responses and identify chlamydial vaccine candidate antigens.