Journal
JOURNAL OF IMMUNOLOGY
Volume 180, Issue 12, Pages 7938-7947Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.180.12.7938
Keywords
-
Categories
Funding
- NIAID NIH HHS [AI 70251, R01 AI070251] Funding Source: Medline
Ask authors/readers for more resources
Influenza virus-specific CD8(+) T cell clonotypes generated and maintained in C57BL/6J mice after respiratory challenge were found previously to distribute unequally between the CD62L(low) effector (T-EM) and CD62L(high) central (T-CM) memory subsets. Defined by the CDR3 beta sequence, most of the prominent TCRs were represented in both the CD62L(high) and CD62L(low) subsets, but there was also a substantial number of diverse, but generally small, CD62L(high)-only clonotypes. The question asked here is how secondary challenge influences both the diversity and the continuity of TCR representation in the T-CM and TEM subsets generated following primary exposure. The experiments use single-cell RT-PCR to correlate clonotypic composition with CD62L phenotype for secondary influenza-specific CD8(+) T cell responses directed at the prominent (DNP366)-N-b and D(b)PA(224) epitopes. In both the acute and long-term memory phases of the recall responses to these epitopes, we found evidence of a convergence of TCR repertoire expression for the CD62L(low) and CD62L(high) populations. In fact, unlike the primary response, there were no significant differences in clonotypic diversity between the CD62L(low) and CD62L(high) subsets. This TCR homogenization for the CD62L(high) and CD62L(low) CD8(+) populations recalled after secondary challenge indicates common origin, most likely from the high prevalence populations in the CD62L(high) central memory set. Our study thus provides key insights into the TCR diversity spectrum for CD62L(high) and CD62L(low) T cells generated from a normal, unmanipulated T cell repertoire following secondary challenge. A better understanding of TCR selection and maintenance has implications for improved vaccine and immunotherapy protocols.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available