期刊
BLOOD
卷 118, 期 2, 页码 319-329出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2010-12-326736
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资金
- Leukaemia Lymphoma Research United Kingdom program [P3379]
- ATTACK [LSHC-CT-2005-018914]
- Medical Research Council [G0700149]
- Experimental Cancer Medicine Center [C34/A7279]
- Medical Research Council Virology Center [G0900950]
- MRC [G0900950, G0902209, G0700149] Funding Source: UKRI
- Medical Research Council [G0902209, G0900950, G0700149] Funding Source: researchfish
We have tested whether affinity-matured TCRs that retain peptide specificity improve the ability of primary human CD8(+) T cells to mount antigen-specific responses. We found that TCR affinity correlated with the speed of T-cell responses. High affinity TCR-antigen interactions rapidly initiated T-cell responses, but low affinity TCR/antigen interactions required longer time periods to elicit the same responses. Within the natural affinity range, increased TCR-to-antigen affinity correlated with improved ability of T cells to recognize low concentration of antigen. However, affinity-matured TCR with 700-fold enhanced affinity for MHC-to-antigen required 100-fold higher antigen-density to initiate T-cell responses than did wild-type TCR. Using modified peptides to reduce the affinity of TCR-to-antigen interaction, we demonstrate that affinity-matured TCRs are not defective, being superior to wild-type TCR in recognizing low concentration of modified pep-tides. These data indicate that enhancing TCR affinity can accelerate the speed of T-cell activation and reduce the ability to recognize low density of MHC-to-peptide antigen. We predict that future studies of the human T-cell repertoire will reveal 2 types of low avidity T cells: fast and slow responders, with high-affinity and low-affinity TCR, respectively. (Blood.2011;118(2):319-329)
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