Quantitating T cell cross-reactivity for unrelated peptide antigens.
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.
Ishizuka
Jeffrey
J
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda MD 20892, USA.
Grebe
Kristie
K
Shenderov
Eugene
E
Peters
Bjoern
B
Chen
Qiongyu
Q
Peng
Yanchun
Y
Wang
Lili
L
Dong
Tao
T
Pasquetto
Valerie
V
Oseroff
Carla
C
Sidney
John
J
Hickman
Heather
H
Cerundolo
Vincenzo
V
Sette
Alessandro
A
Bennink
Jack R
JR
McMichael
Andrew
A
Yewdell
Jonathan W
JW
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
D018984:Epitopes, T-Lymphocyte; D010446:Peptide Fragments; D019151:Peptide Library