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

Viral infections play a role in shaping and maintaining the peripheral T-cell repertoire, as well as ill the initiation Of autoimmune response via mechanisms of molecular mimicry. Ill 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 all infectious agent. The results have implications for vaccine design and for antigen-specific treatment strategies for autoimmune diseases. (C) 2005 Elsevier B.V. All rights reserved.