Cross-reactive responses to modified M158–66 peptides by CD8+ T cells that use noncanonical BV genes can describe unknown repertoires


  • Galina V. Petrova,

  • Jack Gorski

    Corresponding author
    1. The Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI, USA
    • Full correspondence: Dr. Jack Gorski, The Blood Research Institute, BloodCenter of Wisconsin, 8727 Watertown Plank Road, Milwaukee, WI 53226, USA

      Fax: +1-414-937-6284


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Memory T-cell repertoires are populated by clonotypes selected by an individual's history of antigen exposures. Our previous analysis of middle-age CD8+ T-cell memory repertoires to the influenza-derived epitope M158–66, described a network of highly cross-reactive BV19 clonotypes responding to M158–66 and at least one peptide with a conservative amino acid substitution at either of two TCR contact positions. Here, we report that some substitutions abrogate BV19 responses and favor responses with different BV. Cross-reactive T cells using seven other BV families responded to 12 of 13 peptides tested. BV12 clonotypes define the most extensive cross-reactive network that encompasses seven peptides. We generated 3D networks based on the peptides recognized and BV family used and observed a cluster of five peptides that includes M158–66 and another cluster of five peptides that does not include M158–66. The first cluster represents peptides structurally similar to M158–66, and the second represents peptides with more considerable changes in epitope recognition surface. We hypothesize that the second cluster represents the cross-reactive network around another unknown epitope or epitopes. This data supports a model of stable CD8+ T-cell memory networks that include a substantial contribution from cross-reactive T cells.