Human pathogen subversion of antigen presentation

Abstract

Many pathogens have co-evolved with their human hosts to develop strategies for immune evasion that involve disruption of the intracellular pathways by which antigens are bound by class I and class II molecules of the major histocompatibility complex (MHC) for presentation to T cells. Here the molecular events in these pathways are reviewed and pathogen interference is documented for viruses, extracellular and intracellular bacteria and intracellular parasites. In addition to a general review, data from our studies of adenovirus, Chlamydia trachomatis and Coxiella burnetii are summarized. Adenovirus E19 is the first viral gene product described that affects class I MHC molecule expression by two separate mechanisms, intracellular retention of the class I heavy chain by direct binding and by binding to the TAP transporter involved in class I peptide loading. Coxiella and Chlamydia both affect peptide presentation by class II MHC molecules as a result of their residence in endocytic compartments, although the properties of the parasitophorous vacuoles they form are quite different. These examples of active interference with antigen presentation by viral gene products and passive interference by rickettsiae and bacteria are typical of the strategies used by these different classes of pathogens, which need to evade different types of immune responses. Pathogen-host co-evolution is evident in these subversion tactics for which the pathogen crime seems tailored to fit the immune system punishment.

MHC I-dependent antigen presentation is inhibited by poliovirus protein 3A

“…Many mechanisms have been described by which viruses and other pathogens interfere with antigen presentation and T cell activation. Virtually every step of antigen processing and presentation is a target for attack by one pathogen or another (see [11][12][13]. However, this finding is the first example of immune evasion by the induction of a general shutdown in host secretion, a strategy that is available only to pathogens such as nonenveloped viruses that can survive without a functional host secretory apparatus.…”

“…Pathogens such as herpesvirus, adenovirus, cytomegalovirus, and Epstein-Barr virus interfere with antigen presentation by such disparate mechanisms as down-regulation of MHC gene expression, inhibition of antigen peptide processing and translocation into the ER, and sequestration of MHC proteins in the ER (reviewed in refs. [11][12][13]. In other picornaviruses, rhinovirus is known to inhibit antigen-induced T cell proliferation via interactions with intercellular adhesion molecule-1 (14), and the L* protein of Theiler's virus reduces CTL-mediated lysis of infected cells by an unknown mechanism (15).…”

Ex vivo generation of cytotoxic T lymphocytes specific for one or two distinct viruses for the prophylaxis of patients receiving an allogeneic bone marrow transplant

“…18,19 Similar to other human pathogenic viruses, AdV has evolved several mechanisms to escape immune surveillance. [20][21][22] For example, the E1A region proteins block responses to interferons by modifying the IFN-induced transcription of anti-viral genes. In addition, adenoviral proteins encoded by the E3 promoter transcription unit, such as E3-gp19K which is located in the membrane of the endoplasmic reticulum, binds to MHC class I antigens of infected cells and prevents their export from the ER to the cell surface.…”

Regulatory T cell-like responses in deer mice persistently infected with Sin Nombre virus

“…Several contributory mechanisms that should favor the persistence of viruses in host organisms have been identified, including interference with peptide processing, inhibition of MHC biosynthesis, sequestration in immunologically privileged sites, interference with cytokine responses, interference with bone marrow antigen-presenting cell (APC) development, and inhibition of cytolytic responses (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23). However, most of the viruses that use those strategies have large genomes, unlike hantaviruses, that encode polypeptides that target these immunological pathways.…”