title: Cross-reactive responses to modified M1₅₈-₆₆ peptides by CD8⁺ T cells that use noncanonical BV genes can describe unknown repertoires.
abstract: 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 M1(58-66) , described a network of highly cross-reactive BV19 clonotypes responding to M1(58-66)  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 M1(58-66)  and another cluster of five peptides that does not include M1(58-66) . The first cluster represents peptides structurally similar to M1(58-66) , 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.
authors.affiliation: The Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: Galina V
authors.initials: GV
authors.lastname: Petrova
authors.forename: Jack
authors.initials: J
authors.lastname: Gorski
mesh_terms: D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D003001:Cloning, Molecular; D003429:Cross Reactions / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D009980:Influenza A virus / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008875:Middle Aged; D012313:RNA / Q000737:chemistry / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D014763:Viral Matrix Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D000939:Epitopes; C488936:M1 protein, Influenza A virus; D011948:Receptors, Antigen, T-Cell; D014763:Viral Matrix Proteins; D012313:RNA