The polyclonal CD8 T cell response to influenza M158-66 generates a fully connected network of cross-reactive clonotypes to structurally related peptides: a paradigm for memory repertoire coverage of novel epitopes or escape mutants.
The polyclonal CD8 T cell response to influenza M158-66 generates a fully connected network of cross-reactive clonotypes to structurally related peptides: a paradigm for memory repertoire coverage of novel epitopes or escape mutants.
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DOI：
10.4049/jimmunol.1004031
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发表时间：
2011-06-01
期刊：
影响因子：
--
通讯作者：
Gorski J
中科院分区：
文献类型：
--
作者：
Petrova GV;Naumova EN;Gorski J
Cross-reactivity of T cells is defined by recognition of two or more peptide-MHC complexes by the same T cell. Although examples of cross-reactivity have been reported, a detailed examination of cross-reactivity has not been performed. Here we take advantage of the high degree of polyclonality in the BV19 T cell repertoire responding to influenza M158–66 in HLA-A2 individuals to obtain a measure for simple cross-reactivity. We utilize an incremental epitope modulation approach to this question using the HLA-A2 restricted response to influenza M158–66 as the system. In three HLA-A2 adult subjects we identified the BV19 clonotypes in the recall response to the influenza epitope M158–66 and twelve M1 peptides substituted at TCR contact positions 63 or 65. The fraction of cross-reactive clonotypes in the M158–66 repertoire varies from 45% to 58% in the three donors. The extent of cross-reactivity, which is the additional number of peptides recognized by a single clonotype, is as high as six. We summarize the data using a graph theory approach with the cross-reactive clonotypes connecting the different HLA-A2 peptides recognized. The cross-reactive clonotypes form a well-connected network that could provide protection from escape variants. We predict that any new pathogen with an epitope whose shape corresponds to that of the peptides studied here would find a pre-existing repertoire ready to respond to it. We propose that in adult memory repertoires, previously encountered epitopes may have generated similar cross-reactive repertoires.
