High level of cross-reactivity in influenza virus hemagglutinin-specific CD4+ T-cell response: Implications for the initiation of autoimmune response in multiple sclerosis Article

Markovic-Plese, S, Hemmer, B, Zhao, Y et al. (2005). High level of cross-reactivity in influenza virus hemagglutinin-specific CD4+ T-cell response: Implications for the initiation of autoimmune response in multiple sclerosis . JOURNAL OF NEUROIMMUNOLOGY, 169(1-2), 31-38. 10.1016/j.jneuroim.2005.07.014

cited authors

  • Markovic-Plese, S; Hemmer, B; Zhao, Y; Simon, R; Pinilla, C; Martin, R

authors

abstract

  • Viral infections play a role in shaping and maintaining the peripheral T-cell repertoire, as well as in the initiation of autoimmune response via mechanisms of molecular mimicry. In this study, we addressed the flexibility of T-cell receptor (TCR) recognition and the degree of structural and sequence homology required for cross-reactive immune response in the induction of autoimmune response. We studied the extent of cross-reactivity of a CD4+ T-cell clone (TCC) specific for the immunodominant influenza virus hemagglutinin (Flu-HA) peptide derived from a patient with multiple sclerosis (MS) using positional scanning synthetic peptide combinatorial libraries (PS-SCL). We documented cross-reactivity against 14 Flu-HA variants, 11 viral, 15 human, and 3 myelin-derived peptides. Moreover, we identified six naturally occurring peptides with higher stimulatory potency than the native ligand, implicating high potential for cross-reactivity even for a virus-specific memory TCC. Our study demonstrates that flexibility of TCR recognition is present even in a clone with a high degree of TCR specificity for an infectious agent. The results have implications for vaccine design and for antigen-specific treatment strategies for autoimmune diseases. © 2005 Elsevier B.V. All rights reserved.

publication date

  • December 1, 2005

published in

Digital Object Identifier (DOI)

start page

  • 31

end page

  • 38

volume

  • 169

issue

  • 1-2