Molecular T Cell Biology – Basic and Translational Challenges in the Twenty-First Century

Reinherz, Ellis L.; Acuto, Oreste

doi:10.3389/fimmu.2011.00003

Cited by 2 publications

(3 citation statements)

References 61 publications

(61 reference statements)

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“…Almost all currently licensed vaccines against infectious pathogens stimulate generation of antibody production (Bambini and Rappuoli, 2009 ). However, because of recent advances in immunobiology, T cell-based vaccines will soon evolve (Reinherz and Acuto, 2011 ). Engagement of this limb of the immune response is important since CTL target virally transformed cells such as HPV-16 induced tumor cells, whereas antibodies cannot readily do so.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, T cells recognize internal viral proteins that are much less variable than envelope proteins, the targets of neutralizing antibodies. Influenza A is a prime example of a RNA virus where such a T cell approach has the potential to lead to a universal vaccine with coverage of seasonal variants as well as pandemic threats (Reinherz and Acuto, 2011 ).…”

Section: Discussionmentioning

confidence: 99%

“…These are the targets for CD8+ CTL, after all. Because of the pitfalls of indirect functional identification of presumptive tumor antigens (Reinherz and Acuto, 2011 ), a definitive physical identification of tumor antigens by mass spectrometry is important. This can be very challenging, given a limited number of tumor cells available from clinical biopsy samples and potential downregulation of HLA by tumor escape mechanisms (Campo et al, 2010 ).…”

Section: Introductionmentioning

confidence: 99%

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Direct identification of an HPV-16 tumor antigen from cervical cancer biopsy specimens

et al. 2011

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Persistent infection with high-risk human papilloma viruses (HPV) is the worldwide cause of many cancers, including cervical, anal, vulval, vaginal, penile, and oropharyngeal. Since T cells naturally eliminate the majority of chronic HPV infections by recognizing epitopes displayed on virally altered epithelium, we exploited Poisson detection mass spectrometry (MS3) to identify those epitopes and inform future T cell-based vaccine design. Nine cervical cancer biopsies from HPV-16 positive HLA-A*02 patients were obtained, histopathology determined, and E7 oncogene PCR-amplified from tumor DNA and sequenced. Conservation of E7 oncogene coding segments was found in all tumors. MS3 analysis of HLA-A*02 immunoprecipitates detected E711–19 peptide (YMLDLQPET) in seven of the nine tumor biopsies. The remaining two samples were E711–19 negative and lacked the HLA-A*02 binding GILT thioreductase peptide despite possessing binding-competent HLA-A*02 alleles. Thus, the conserved E711–19 peptide is a dominant HLA-A*02 binding tumor antigen in HPV-16 transformed cervical squamous and adenocarcinomas. Findings that a minority of HLA-A*02:01 tumors lack expression of both E711–19 and a peptide from a thioreductase important in processing of cysteine-rich proteins like E7 underscore the value of physical detection, define a potential additional tumor escape mechanism and have implications for therapeutic cancer vaccine development.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Direct identification of an HPV-16 tumor antigen from cervical cancer biopsy specimens

et al. 2011

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Mechanical regulation of T‐cell functions

Chen

Zhu

2013

Immunological Reviews

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Summary T cells are key players of the mammalian adaptive immune system. They experience different mechanical microenvironments during their life cycles, from the thymus, secondary lymph organs, and peripheral tissues that are free of externally applied force but display variable substrate rigidities, to the blood and lymphatic circulation systems where complicated hydrodynamic forces are present. Regardless of whether T cells are subject to external forces or generate their own internal forces, they response and adapt to different biomechanical cues to modulate their adhesion, migration, trafficking, and triggering of immune functions through mechanical regulation of various molecules that bear force. These include adhesive receptors, immunoreceptors, motor proteins, cytoskeletal proteins, and their associated molecules. Here we discuss the forces acting on various surface and cytoplasmic proteins of a T cell in different mechanical milieus. We review existing data on how force regulates protein conformational changes and interactions with counter molecules, including integrins, actin, and the T-cell receptor, and how each relates to T-cell functions.

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Molecular T Cell Biology – Basic and Translational Challenges in the Twenty-First Century

Cited by 2 publications

References 61 publications

Direct identification of an HPV-16 tumor antigen from cervical cancer biopsy specimens

Direct identification of an HPV-16 tumor antigen from cervical cancer biopsy specimens

Mechanical regulation of T‐cell functions

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