CD8⁺T cells recognize an inclusion membrane-associated protein from the vacuolar pathogenChlamydia trachomatis

Abstract

During infection with Chlamydia trachomatis, CD8 ؉ T cells are primed, even though the bacteria remain confined to a host cell vacuole throughout their developmental cycle. Because CD8 ؉ T cells recognize antigens processed from cytosolic proteins, the Chlamydia antigens recognized by these CD8 ؉ T cells very likely have access to the host cell cytoplasm during infection. The identity of these C. trachomatis proteins has remained elusive, even though their localization suggests they may play important roles in the biology of the organism. Here we use a retroviral expression system to identify Cap1, a 31-kDa protein from C. trachomatis recognized by protective CD8 ؉ T cells. Cap1 contains no strong homology to any known protein. Immunofluorescence microscopy by using Cap1-specific antibody demonstrates that this protein is localized to the vacuolar membrane. Cap1 is virtually identical among the human C. trachomatis serovars, suggesting that a vaccine incorporating Cap1 might enable the vaccine to protect against all C. trachomatis serovars. The identification of proteins such as Cap1 that associate with the inclusion membrane will be required to fully understand the interaction of C. trachomatis with its host cell.

Molecular Mimicry of an HLA-B27-derived Ligand of Arthritis-linked Subtypes with Chlamydial Proteins

“…C. trachomatis has evolved mechanisms to evade CTL recognition and killing of infected cells through degrading the transcription factor RFX5, which is needed for constitutive and IFN-␥-induced MHC class I expression, leading to a severe drop of these molecules from the cell surface 24 h or later after infection (55,56). Despite this, CTL responses can be elicited against C. trachomatis-infected cells (57,58), presumably due to bacterial antigen processing and presentation early after infection. In addition, CD8 ϩ T-cells recognizing HLA-B27-restricted chlamydial peptides have been identified from the synovial fluid of Chlamydia-induced ReA patients and from transgenic mice (59).…”

Identification of naturally processed CD8 T cell epitopes from prostein, a prostate tissue‐specific vaccine candidate

“…Recombinant retroviruses were generated using the Phoenix-Ampho packaging system and the vectors pBiB [31], including a polylinker and the blasticidin D-selectable marker, or pBiZ, derived from pBiB in which the blasticidin S gene has been replaced with the selectable marker for zeocin resistance (S. Fling, Corixa Corporation, unpublished).…”

Immune-mediated control of Chlamydia infection

“…Although Chlamydia are confined to the inclusion during the intracellular stages of the developmental cycle, a number of Chlamydia proteins have access to the host cytosol. These include proteins that are secreted into the cytoplasm (Zhong et al, 2001;Clifton et al, 2004) as well as inclusion membrane proteins that have domains which extend into the cytosol of the host cell (Bannantine et al, 2000;Fling et al, 2001). Chlamydia proteins that have access to the cytosol have been demonstrated to serve as CD8 + T-cell antigens (Fling et al, 2001;Starnbach et al, 2003).…”