Journal
JOURNAL OF IMMUNOLOGY
Volume 183, Issue 7, Pages 4337-4345Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.0901607
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Funding
- Intramural Research, National Institute of Allergy and Infectious Diseases
- Medical Research Council Human Immunology Unit
- Cancer Research UK [C399/A2291]
- Medical Research Council [MC_U137884177, G0600520, MC_U137884181] Funding Source: researchfish
- MRC [G0600520, MC_U137884177, MC_U137884181] Funding Source: UKRI
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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 (similar to 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. The Journal of Immunology, 2009, 183: 4337-4345.
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