Degenerate TCR recognition and dual DR2 restriction of autoreactive T cells: implications for the initiation of the autoimmune response in multiple sclerosis.

European Journal of Immunology
Xin ZhangSilva Markovic-Plese

Abstract

TCR degeneracy may facilitate self-reactive T cell activation and the initiation of an autoimmune response in multiple sclerosis (MS). MHC class II alleles of the DR2 haplotype DR2a (DRB5*0101) and DR2b (DRB1*1501) are associated with an increased risk for MS in Caucasian populations. In order to selectively expand and characterize T cells with a high degree of TCR degeneracy that recognize peptides in the context of disease-associated DR2 alleles, we developed DR2-anchored peptide mixtures (APM). We report here that DR2-APM have a high stimulatory potency and can selectively expand T cells with a degenerate TCR (TCR(deg)). Due to the low concentration of individual peptides in the mixtures, T cell clones' proliferative response to DR2-APM implies that multiple peptides stimulate the TCR, which is a characteristic of TCR(deg). The frequency of DR2-APM-reactive T cells is significantly higher in MS patients than in healthy controls, suggesting that they may play a role in the development of the autoimmune response in MS. DR2-APM-reactive cells have a dual DR2 restriction: they recognize DR2-APM in the context of both DR2a and DR2b molecules. The DR2-APM-reactive cells' IL-17 secretion, together with cross-reactivity against myel...Continue Reading

References

Feb 1, 1991·Journal of Neuroscience Research·W F HickeyH Kimura
Jan 7, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·B HemmerR Martin
May 22, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·S K JoshiV S Chauhan
Dec 13, 2002·Brain : a Journal of Neurology·Paolo A MuraroRoland Martin
Jan 7, 2003·Nature Medicine·Clemencia PinillaRichard A Houghten
Mar 9, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Bibiana BielekovaRoland Martin
Mar 24, 2004·Molecular Immunology·Jacqueline Shukaliak QuandtRoland Martin
Jul 22, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Marcin P MyckoDavid A Hafler
Aug 23, 2005·Journal of Neuroimmunology·Elisabetta PratRoland Martin
Jan 21, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mireia SospedraRoland Martin
Feb 17, 2007·European Journal of Immunology·Guifang Cai, David A Hafler

❮ Previous
Next ❯

Citations

Sep 3, 2008·Journal of Clinical Immunology·Cristina Maria CostantinoDavid A Hafler
May 16, 2009·Nature Reviews. Immunology·Joan Goverman
Mar 12, 2013·Antioxidants & Redox Signaling·Djordje Miljković, Ivan Spasojević
Mar 17, 2010·Journal of Neuroimmunology·Makoto HirotaniHidenao Sasaki
Dec 5, 2015·Frontiers in Immunology·Marion SalouDavid-Axel Laplaud
Nov 19, 2011·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·T VirtanenM Rytkönen-Nissinen
Mar 20, 2009·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Silva Markovic-Plese
Apr 22, 2008·European Journal of Immunology·Piet Stinissen, Niels Hellings
Mar 7, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Xin ZhangSilva Markovic-Plese
Sep 29, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Vinod S RamgolamSilva Markovic-Plese
Aug 28, 2021·Brain Sciences·Aleksandra Damasiewicz-BodzekKrystyna Tyrpień-Golder

❮ Previous
Next ❯

Related Concepts

Related Feeds

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.