We previously identified 18 stimulatory Chlamydia trachomatis major outer membrane protein (MOMP) peptides containing at least 23 epitopes presented with various HLA class II allotypes. Only one peptide contained an epitope localized in a variable segment (VS2). Continued studies reported here identified a total of five VS peptides containing T-cell epitopes that are distributed among MOMPs VS1, VS2, and VS4. Only MOMP-primed T-cell cultures from subjects infected with serovar E responded to the serovar E VS peptides, while the response of such cultures to constant-segment peptides was independent of the infecting serovar. Furthermore, MOMP-primed T cells proliferated in response only to the VS peptides encoded in serovar E but not to the corresponding peptides derived from serovar F, I, or J, confirming that these responses were serovar specific.Chlamydia trachomatis causes ocular and genital tract infections worldwide. In the United States, the annual cost of treating sexually transmitted diseases caused by C. trachomatis is billions of dollars (9). Effective preventive measures against C. trachomatis infections are not yet available, due in part to insufficient understanding of human immune responses to C. trachomatis. Evidence for protective immunity against C. trachomatis is scant and inconclusive. However, earlier studies have suggested that short-lived immunity develops after an episode of chlamydial infection (1,10,12) and that protection may be serovar specific (reviewed in reference 8); while reinfection with C. trachomatis is common, it is usually not with serovars of preceding infections. Consequently, many immunological studies of human genital tract infections have been focused on the major outer membrane protein (MOMP) because C. trachomatis serovars are defined by serological variation in this protein. In humans, MOMP elicits C. trachomatisneutralizing antibodies that recognize its surface-exposed variable segments (VSs), where amino acid sequences vary substantially among serovars (4). Therefore, some have speculated that B-cell responses directed toward serovar-specific epitopes located in VSs of MOMP are a critical component of protective immunity (16)(17)(18).Because of the role of T helper (Th) cells in priming and maintaining B-cell responses, we have investigated HLA class II-restricted Th cell responses to MOMP in humans genitally infected with C. trachomatis, focusing on commonly involved serovar E. The main results of our first study (14) were that (i) in vitro priming of peripheral blood mononuclear cells (PBMC) with MOMP yielded MOMP-specific Th cell cultures from 83% of serovar E-infected subjects; (ii) proliferative responses of T-MOMPЈ cultures to synthetic peptides localized at least 23 Th cell epitopes, and T-MOMPЈ cultures from most subjects responded to multiple epitopes; (iii) multiple HLA-DR and other HLA class II molecules were used to present the MOMP epitopes to the Th cells; and (iv) remarkably, 22 of the 23 epitopes were distributed among the five MOMP constant segments ...

HLA class I-restricted CD8+ CTLs specific for the major outer membrane protein (MOMP) of Chlamydia trachomatis are present in the peripheral blood of humans who acquired genital tract infections with the organism. Three HLA-A2-restricted epitopes and two HLA-B51-restricted epitopes were identified in serovar E-MOMP. One of the five epitopes spans a variable segment of MOMP and is likely a serovar E-specific epitope. The other four epitopes are localized in constant segments and are C. trachomatis species specific. CTL populations specific for one or more of the four constant segment epitopes were isolated from all 10 infected subjects tested, regardless of infecting serovars, but from only one of seven uninfected subjects tested. The CTLs failed to recognize corresponding peptides derived from Chlamydia pneumoniae MOMP, further suggesting that they indeed resulted from genital tract infections with C. trachomatis. Significantly, ME180 human cervical epithelial cells productively infected with C. trachomatis were killed by the MOMP peptide-specific CTLs. Further investigations of the ability of such CTLs to lyse normal infected epithelial cells and their presence at inflamed sites in the genital tract will help understand the protective or pathological role of CTLs in chlamydial infections. The MOMP CTL epitopes may be explored as potential components of a subunit vaccine against sexually transmitted diseases caused by C. trachomatis. Moreover, the knowledge provided here will facilitate studies of HLA class I pathways of chlamydial Ag processing and presentation in physiologically relevant human APCs.