T Cell Receptor Gene Rearrangement Lineage Analysis Reveals Clues for the Origin of Highly Restricted Antigen-specific Repertoires
| Autor: | Anne Aublin, Philippe Guillaume, Janet L. Maryanski, Abdelbasset Hamrouni |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
sequence analysis
Cell division Receptors Antigen T-Cell alpha-beta T cell Immunology receptors chemical and pharmacologic phenomena Locus (genetics) CD8-Positive T-Lymphocytes Biology Polymerase Chain Reaction Article Recombination-activating gene Mice antigen Antigen medicine Animals Immunology and Allergy Cell Lineage Amino Acid Sequence Antigens Gene Rearrangement beta-Chain T-Cell Antigen Receptor Gene Recombination Genetic Genetics Base Sequence Models Genetic Repertoire T-cell receptor hemic and immune systems CD8+ T lymphocytes medicine.anatomical_structure Female Gene Rearrangement alpha-Chain T-Cell Antigen Receptor Sequence Alignment |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| DOI: | 10.1084/jem.20021945 |
| Popis: | Due to ordered, stage-specific T cell receptor (TCR)-beta and -alpha locus gene rearrangements and cell division during T cell development, a given, ancestral TCR-beta locus VDJ rearrangement might be selected into the mature T cell repertoire as a small cohort of "half-sibling" progeny expressing identical TCR-beta chains paired with different TCR-alpha chains. The low frequency of such a cohort relative to the total alphabeta TCR repertoire precludes their direct identification and characterization in normal mice. We considered it possible that positive selection constraints might limit the diversity of TCR-alpha chains selected to pair with beta chains encoded by an ancestral VDJ-beta rearrangement. If so, half-sibling T cells expressing structurally similar, but different TCR-alpha chains might recognize the same foreign antigen. By single cell polymerase chain reaction analysis of antigen-specific TCRs selected during a model anti-tumor response, we were able to identify clusters of T cells sharing identical VDJ-beta rearrangements but expressing different TCR-alpha chains. The amplification of residual DJ-beta rearrangements as clonal markers allowed us to track T cells expressing different TCR-alpha chains back to a common ancestral VDJ-beta rearrangement. Thus, the diversity of TCR-alpha's selected as partners for a given VDJ-beta rearrangement into the mature TCR repertoire may indeed be very limited. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|