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Evolution of Antigen-specific T Cell Receptors In Vivo: Preimmune and Antigen-driven Selection of Preferred Complementarity-determining Region 3 (CDR3) Motifs
| Content Provider | Scilit |
|---|---|
| Author | Heyzer-Williams, Louise J. Mc Panus, Joanne Fanelli Mikszta, John A. Heyzer-Williams, Michael G. Mc |
| Copyright Year | 1999 |
| Description | Antigen (Ag)-driven selection of helper T cells (Th) in normal animals has been difficult to study and remains poorly understood. Using the major histocompatibility complex class II– restricted murine response to pigeon cytochrome c (PCC), we provide evidence for both preimmune and Ag-driven selection in the evolution of Ag-specific immunity in vivo. Before antigenic challenge, most Vα11+Vβ3+ Th (70%) express a critical complementarity-determining region 3 (CDR3) residue (glutamic acid at TCR-α93) associated with PCC peptide contact. Over the first 5 d of the primary response, PCC-responsive Vα11+Vβ3+ Th expressing eight preferred CDR3 features are rapidly selected in vivo. Clonal dominance is further propagated through selective expansion of the PCC-specific cells with T cell receptor (TCR) of the “best fit.” Ag-driven selection is complete before significant emergence of the germinal center reaction. These data argue that thymic selection shapes TCR-α V region bias in the preimmune repertoire; however, Ag itself and the nongerminal center microenvironment drive the selective expansion of clones with preferred TCR that dominate the response to Ag in vivo. |
| Related Links | http://jem.rupress.org/content/189/11/1823.full.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193074/pdf http://jem.rupress.org/content/jem/189/11/1823.full.pdf |
| Ending Page | 1838 |
| Page Count | 16 |
| Starting Page | 1823 |
| DOI | 10.1084/jem.189.11.1823 |
| Journal | The Journal of experimental medicine |
| Issue Number | 11 |
| Volume Number | 189 |
| Language | English |
| Publisher | Rockefeller University Press |
| Publisher Date | 1999-06-07 |
| Access Restriction | Open |
| Subject Keyword | Immunology Immunologic Memory Clonal Maturation Antigen-specific Immunity Helper T Cells T Cell Receptor Journal: The Journal of experimental medicine (Vol- 189, Issue- 11) |
| Content Type | Text |