期刊
JOURNAL OF IMMUNOLOGY
卷 181, 期 1, 页码 649-659出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.181.1.649
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资金
- Intramural NIH HHS [Z01 AI000814-11, Z01 AI000542-20, Z01 AI001014-01] Funding Source: Medline
The action of TdT on mouse TCR genes accounts for similar to 90% of T cell repertoire diversity. We report that in TdT(-/-) mice, total TCD8+ responses to influenza and vaccinia viruses are reduced by similar to 30% relative to wild-type mice. We find that TCD8+ responses to three subdominant influenza virus determinants are reduced to background values in TdT(-/-) mice while responses to three immunodominant determinants undergo a major reshuffling. A similar reshuffling occurs in TCD8+ responses to immunodominant vaccinia virus determinants, and is clearly based on broad differences in TCR family usage and CDR3 length between wild-type and TdT(-/-) mice. These findings demonstrate that TdT plays a critical role in the magnitude and breadth of anti-viral TCD8+ responses toward individual determinants and suggests that germline TCR repertoire bias toward the most dominant determinants is a major factor in establishing immunodominance hierarchies.
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