Tapasin shapes immunodominance hierarchies according to the kinetic stability of peptide-MHC class I complexes

European Journal of Immunology
Stephen M ThirdboroughTim Elliott

Abstract

Peptide loading of MHC class I molecules involves multiple cofactors including tapasin. We showed previously in vitro that tapasin edits the peptide repertoire by favoring the binding of peptides with slow dissociation rates. Here, using tapasin-deficient mice and a DNA vaccine that primes directly, we confirm that tapasin establishes hierarchical responses in vivo according to peptide-MHC stability. In contrast, this hierarchy is lost when the peptides are cross-presented via an alternative DNA vaccine. By regulating transgene expression, we found that the dominant response modifier was antigen persistence. Our findings reveal strategies for activating T cells against low-affinity peptides, of potential importance for patients with repertoires narrowed by deletional tolerance.

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Citations

Apr 27, 2011·The Journal of Biological Chemistry·Gustav RoderKajsa Paulsson
Jun 29, 2011·Journal of Acquired Immune Deficiency Syndromes : JAIDS·David FriedrichHelen Horton
Mar 13, 2014·Laboratory Investigation; a Journal of Technical Methods and Pathology·Xiaohua ChenGuoqing Zang
Oct 27, 2011·Immunology Letters·Dilip ShresthaAttila Jenei
Oct 18, 2011·European Journal of Immunology·Ian GaleaStephen M Thirdborough
Mar 28, 2013·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Shirin AshrafSalim I Khakoo
Dec 18, 2009·European Journal of Immunology·P V K PraveenSebastian Springer
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Oct 21, 2015·Scientific Reports·Alistair BaileyTim Elliott
Aug 13, 2011·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Malgorzata Anna GarstkaSebastian Springer
Jul 19, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Amabel C L TanDavid C Jackson
Dec 2, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Denise S M BoulangerTim Elliott

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