TITLE

Attenuated T Cell Responses to a High-Potency Ligand In Vivo

AUTHOR(S)
Corse, Emily; Gottschalk, Rachel A.; Krogsgaard, Michelle; Allison, James P.
PUB. DATE
September 2010
SOURCE
PLoS Biology;Sep2010, Vol. 8 Issue 9, p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
αβ T cell receptor (TCR) recognition of foreign peptides bound to major histocompatibility complex (pMHC) molecules on the surface of antigen presenting cells is a key event in the initiation of adaptive cellular immunity. In vitro, high-affinity binding and/or long-lived interactions between TCRs and pMHC correlate with high-potency T cell activation. However, less is known about the influence of TCR/pMHC interaction parameters on T cell responses in vivo. We studied the influence of TCR/pMHC binding characteristics on in vivo T cell immunity by tracking CD4+ T cell activation, effector, and memory responses to immunization with peptides exhibiting a range of TCR/pMHC half-lives and in vitro T cell activation potencies. Contrary to predictions from in vitro studies, we found that optimal in vivo T cell responses occur to ligands with intermediate TCR/pMHC half-lives. The diminished in vivo responses we observed to the ligand exhibiting the longest TCR/pMHC half-life were associated with attenuation of intracellular signaling, expansion, and function over a broad range of time points. Our results reveal a level of control over T cell activation in vivo not recapitulated in in vitro assays and highlight the importance of considering in vivo efficacy of TCR ligands as part of vaccine design.
ACCESSION #
55424969

 

Related Articles

  • Molecular and structural determinants of adamantyl susceptibility to HLA-DRs allelic variants: an in silico approach to understand the mechanism of MLEs. Zaheer-ul-Haq; Khan, Waqasuddin // Journal of Computer-Aided Molecular Design;Jan2011, Vol. 25 Issue 1, p81 

    Class II major histocompatibility complex (MHC II) molecules as expressed by antigen-presenting cells are heterodimeric cell-surface glycoprotein receptors that are fundamental in initiating and propagating an immune response by presenting tumor-associated antigenic peptides to CD4/T cells. The...

  • NetMHCIIpan- 3. 0, a common pan-specific MHC class II prediction method including all three human MHC class II isotypes, HLA-DR, HLA-DP and HLA-DQ. Karosiene, Edita; Rasmussen, Michael; Blicher, Thomas; Lund, Ole; Buus, Søren; Nielsen, Morten // Immunogenetics;Oct2013, Vol. 65 Issue 10, p711 

    Major histocompatibility complex class II (MHCII) molecules play an important role in cell-mediated immunity. They present specific peptides derived from endosomal proteins for recognition by T helper cells. The identification of peptides that bind to MHCII molecules is therefore of great...

  • TCR–peptide–MHC interactions in situ show accelerated kinetics and increased affinity. Huppa, Johannes B.; Axmann, Markus; Mörtelmaier, Manuel A.; Lillemeier, Björn F.; Newell, Evan W.; Brameshuber, Mario; Klein, Lawrence O.; Schütz, Gerhard J.; Davis, Mark M. // Nature;2/18/2010, Vol. 463 Issue 7283, p963 

    The recognition of foreign antigens by T lymphocytes is essential to most adaptive immune responses. It is driven by specific T-cell antigen receptors (TCRs) binding to antigenic peptide–major histocompatibility complex (pMHC) molecules on other cells. If productive, these interactions...

  • The PickPocket method for predicting binding specificities for receptors based on receptor pocket similarities: application to MHC-peptide binding. Hao Zhang; Ole Lund; Morten Nielsen // Bioinformatics;May2009, Vol. 25 Issue 10, p1293 

    Motivation: Receptor–ligand interactions play an important role in controlling many biological systems. One prominent example is the binding of peptides to the major histocompatibility complex (MHC) molecules controlling the onset of cellular immune responses. Thousands of MHC allelic...

  • Detection and Characterization of Cellular Immune Responses Using Peptide --MHC Microarrays. Soen, Yoav; Chen, Daniel S.; Kraft, Daniel L.; Davis, Mark M.; Brown, Patrick O. // PLoS Biology;Dec2003, Vol. 1 Issue 3, p429 

    The detection and characterization of antigen-specific T cell populations is critical for understanding the development and physiology of the immune system and its responses in health and disease. We have developed and tested a method that uses arrays of peptide-MHC complexes for the rapid...

  • Characterization of MHC Ligands for Peptide Based Tumor Vaccination. Klug, Felix; Miller, Matthias; Schmidt, Hans-Henning; Stevanović, Stefan // Current Pharmaceutical Design;10/1/2009, Vol. 15 Issue 28, p3221 

    Short peptides derived from cellular proteins may escape complete destruction during protein catabolism and finally serve as a showcase in the immune system. Exposed at the cell surface to scrutiny by T cells, MHC:peptide complexes mediate a highly specific and immediate information transfer...

  • Properties of MHC Class I Presented Peptides That Enhance Immunogenicity. Calis, Jorg J. A.; Maybeno, Matt; Greenbaum, Jason A.; Weiskopf, Daniela; De Silva, Aruna D.; Sette, Alessandro; Keşmir, Can; Peters, Bjoern // PLoS Computational Biology;Oct2013, Vol. 9 Issue 10, p1 

    T-cells have to recognize peptides presented on MHC molecules to be activated and elicit their effector functions. Several studies demonstrate that some peptides are more immunogenic than others and therefore more likely to be T-cell epitopes. We set out to determine which properties cause such...

  • Degenerate T-cell Recognition of Peptides on MHC Molecules Creates Large Holes in the T-cell Repertoire. Calis, Jorg J. A.; De Boer, Rob J.; Keşmir, Can // PLoS Computational Biology;Mar2012, Vol. 8 Issue 3, p1 

    The cellular immune system screens peptides presented by host cells on MHC molecules to assess if the cells are infected. In this study we examined whether the presented peptides contain enough information for a proper self/nonself assessment by comparing the presented human (self) and bacterial...

  • TCR affinity for thymoproteasome-dependent positively selecting peptides conditions antigen responsiveness in CD8+ T cells. Takada, Kensuke; Van Laethem, Francois; Xing, Yan; Akane, Kazuyuki; Suzuki, Haruhiko; Murata, Shigeo; Tanaka, Keiji; Jameson, Stephen C; Singer, Alfred; Takahama, Yousuke // Nature Immunology;Oct2015, Vol. 16 Issue 10, p1069 

    In the thymus, low-affinity T cell antigen receptor (TCR) engagement facilitates positive selection of a useful T cell repertoire. Here we report that TCR responsiveness of mature CD8+ T cells is fine tuned by their affinity for positively selecting peptides in the thymus and that optimal TCR...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics