Molecular analysis of immunoglobulins M and G immune response to protein antigens of Treponema pallidum in human syphilis

Abstract

Protein antigens of Treponema pallidum precipitated by immunoglobulin M (IgM) and IgG antibodies of sera from patients with untreated primary and secondary syphilis as well as treated secondary syphilis were characterized on a molecular basis. T. pallidum was labeled internally with [35S]methionine and solubilized in 0.1% sodium dodecyl sulfate-1% Triton X-100. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis on 12.5% gels followed by autoradiography revealed 32 distinct proteins with molecular weights between 13,500 and 200,000. Twenty-three proteins of T. pallidum with molecular weights between 15,500 and 115,000 were identified as antigens by double antibody radioimmunoprecipitation with IgM and IgG antibodies of sera from syphilitic patients. The molecular analysis of the IgM and IgG immune response to T. pallidum in human syphilis is in accord with earlier immunological observations. Finally, utilizing syphilitic human sera, we characterized 15 protein antigens of T. pallidum that are common to Treponema phagedenis by partial absorption of IgM and IgG antibodies with an ultrasonicate of T. phagedenis.

Circulating immune complexes in experimental syphilis and their relation to immunological response against Treponema pallidum

“…The immunoglobulin in the CIC was similar to the antibodies produced during a syphilitic infection [18]. It would seem to be IgM at the beginning of the disease and IgG later in rabbit syphilis.…”

Immunological Studies on Venereal Spirochetosis of Rabbits (Rabbit Syphilis)

“…The antibodies against the T . pallidum flagellar proteins, predominant 37 kDa and 35 kDa proteins, have been detected in the syphilitic human sera (MOSKOPHIDIS and MULLER, 1984), suggestive of their effective immunogens in vivo. In this study, however, no specific reactions were observed on the proteins with molecular sizes of 30-40 kDa of T. pallidum strain Nichols.…”

Cytotoxic T‐lymphocyte escape viral variants: how important are they in viral evasion of immune clearance in vivo?

“…Thus, not only the strength of the CTL response to a particular epitope hut also the immunodominance of this response will have a great impact on the likelihood that escape mutations will be selected for within the epitope. Escape mutations in subdominant or even co-dominant CTL epitopes may confer such a shght selective advantage on the viral variants bearing them (whose replication will still he controlled by the more dominant or co-dominant CTL responses in the host (58,59)) that they may never emerge in vivo. Virus rephcation must clearly be ongoing for viral variants to be generated and selected.…”

“…That this certainly can occur bas been illustrated in experiments performed in the LCMV model system, CTL clones directed against the three most dominant epitopes recognized during the antiviral CTL response in C57BL/6 mice were used to select in vitro for LCMV variants bearing escape-conferring mutations in one, two or all three of these epitopes (81)(82)(83). Wben CS7BL/6 mice were infected with tbe mutant viruses, they mounted CTL responses to subdominant epitopes including epitope(s) in the viral polymerase wbich are not readily apparent during tbe response to wild-type virus, but the responses driven by the in vitro-generated escape viral variants controlled virus replication less efficiently than the response to wild-type virus (58,59). These experiments indicate tbat although tbe immnne response is extremely plastic, its capacity to evolve to efficiently contain the replication of escape mutant viruses may be limited, particularly in inbred mice where the diversity of MHC alleles is more restricted than in the outbred human population.…”