Journal
JOURNAL OF CLINICAL INVESTIGATION
Volume 116, Issue 5, Pages 1443-1456Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI27804
Keywords
-
Categories
Funding
- NIAID NIH HHS [AI054455, AI46578, R01 AI046578, R01 AI054455] Funding Source: Medline
- NIAMS NIH HHS [AR35506, R01 AR035506] Funding Source: Medline
- NIDDK NIH HHS [DK52530] Funding Source: Medline
Ask authors/readers for more resources
Why some virus-specific CD8 TCR repertoires are diverse and others restricted or oLigoclonal has been unknown. We show here that oligoclonality and extreme clonal dominance can be a consequence ofT cell crossreactivity. Lymphocytic choriomeningitis virus (LCMV) and Pichinde virus (PV) encode NP205-212 epitopes that induce different but highly cross-reactive diverse TCR repertoires. Homologous viral challenge of immune mice only slightly skewed the repertoire and enriched for predictable TCR motifs. However, heterologous viral challenge resulted in a narrow oligoclonal repertoire with dominant clones with unpredictable TCR sequences. This shift in clonal dominance varied with the private, i.e., unique, specificity of the host's TCR repertoire and was simulated using affinity-based computer models. The skewing differences in TCR repertoire following homologous versus heterologous challenge were observed within the same private immune system in mice adoptively reconstituted with memory CD8 T cell pools from the same donor. Conditions driving oligoclonality resulted in an LCMV epitope escape variant in vivo resembling the natural Lassa virus sequence. Thus, T cell oligoclonality, including extremes in clonal dominance, may be a consequence ofheterologous immunity and lead to viral escape. This has implications for the design of pepdde-based vaccines, which might unintentionally prime for skewed TCR responses to cross-reactive epitopes.
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