Immunopathology that is caused by re-infection with Chlamydia trachomatis is very common in humans despite regular responses to multiple, often conserved, antibody and T cell epitopes. Recurrent mutations that disrupt T cell epitopes in the major outer membrane protein in clinical isolates and the reduced transcription of HLA genes by infected cells may be evidence for pathogen evasion of protective immune responses. Subunit vaccines containing recently discovered clusters of T cell epitopes in the major outer membrane protein that are presented with diverse HLA allotypes may allow widespread protective immunization while avoiding the suppression of lasting immunity that occurs by unknown mechanisms associated with infection.