title: Quantitating T cell cross-reactivity for unrelated peptide antigens.
abstract: Quantitating the frequency of T cell cross-reactivity to unrelated peptides is essential to understanding T cell responses in infectious and autoimmune diseases. Here we used 15 mouse or human CD8+ T cell clones (11 antiviral, 4 anti-self) in conjunction with a large library of defined synthetic peptides to examine nearly 30,000 TCR-peptide MHC class I interactions for cross-reactions. We identified a single cross-reaction consisting of an anti-self TCR recognizing a poxvirus peptide at relatively low sensitivity. We failed to identify any cross-reactions between the synthetic peptides in the panel and polyclonal CD8+ T cells raised to viral or alloantigens. These findings provide the best estimate to date of the frequency of T cell cross-reactivity to unrelated peptides ( approximately 1/30,000), explaining why cross-reactions between unrelated pathogens are infrequently encountered and providing a critical parameter for understanding the scope of self-tolerance.
authors.affiliation: Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda MD 20892, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Ishizuka
authors.forename: Kristie
authors.initials: K
authors.lastname: Grebe
authors.forename: Eugene
authors.initials: E
authors.lastname: Shenderov
authors.forename: Bjoern
authors.initials: B
authors.lastname: Peters
authors.forename: Qiongyu
authors.initials: Q
authors.lastname: Chen
authors.forename: Yanchun
authors.initials: Y
authors.lastname: Peng
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.forename: Tao
authors.initials: T
authors.lastname: Dong
authors.forename: Valerie
authors.initials: V
authors.lastname: Pasquetto
authors.forename: Carla
authors.initials: C
authors.lastname: Oseroff
authors.forename: John
authors.initials: J
authors.lastname: Sidney
authors.forename: Heather
authors.initials: H
authors.lastname: Hickman
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cerundolo
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sette
authors.forename: Jack R
authors.initials: JR
authors.lastname: Bennink
authors.forename: Andrew
authors.initials: A
authors.lastname: McMichael
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Yewdell
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology / Q000821:virology; D045744:Cell Line, Tumor; D002999:Clone Cells; D003429:Cross Reactions; D045142:Cross-Priming / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000819:agonists / Q000276:immunology* / Q000378:metabolism*; D019151:Peptide Library; D011237:Predictive Value of Tests; D011485:Protein Binding / Q000276:immunology
chemical_list: D018984:Epitopes, T-Lymphocyte; D010446:Peptide Fragments; D019151:Peptide Library