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Immunology and Infectious Disease

Washington University in St. Louis

Theses/Dissertations

MHCI

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Full-Text Articles in Life Sciences

Viral Mhc Class I Evasion Affects Anti-Viral T Cell Development And Responses, Elvin James Lauron Aug 2018

Viral Mhc Class I Evasion Affects Anti-Viral T Cell Development And Responses, Elvin James Lauron

Arts & Sciences Electronic Theses and Dissertations

Cytotoxic CD8+ T cells (CTLs) play a critical role in protective immunity against viruses, a fact underscored by the evolution of viral CTL evasion mechanisms. For instance, many viruses commonly target the major histocompatibility complex class I (MHCI) antigen presentation pathway to prevent CTLs from recognizing infected cells. A striking example of this is cowpox virus (CPXV), which interferes with MHCI antigen presentation through two distinct mechanisms. One mechanism of CPXV-mediated MHCI inhibition is to retain MHCI molecules in the endoplasmic reticulum (ER). The second mechanism is to prevent antigen peptide loading onto MHCI molecules. When combined these mechanisms result …


Structural Mechanism Of Orthopoxvirus Sabotage Of Mhci Antigen Presentation, William Howard Mccoy Iv May 2013

Structural Mechanism Of Orthopoxvirus Sabotage Of Mhci Antigen Presentation, William Howard Mccoy Iv

All Theses and Dissertations (ETDs)

Immunomodulatory proteins that subvert major histocompatibility complex class I: MHCI) antigen presentation can help viruses to evade cytotoxic T-lymphocyte: CTL) detection and clearance. Cowpox virus, like other orthopoxvirus family members, is a large DNA virus, whose genomic termini encode numerous immunomodulatory genes, including two ER-resident MHCI saboteurs: CPXV012 and CPXV203). CPXV012 inhibits peptide loading of MHCI within the peptide-loading complex: PLC), while CPXV203 inhibits surface expression of both murine and human MHCI through the use of a C-terminal ER-retention sequence: KTEL). An association: direct or indirect) between CPXV203 and MHCI was first demonstrated in pull-down experiments. This doctoral work explores …