| First Author | Culberson EJ | Year | 2022 |
| Journal | J Immunol | Volume | 209 |
| Issue | 1 | Pages | 93-98 |
| PubMed ID | 35697383 | Mgi Jnum | J:344982 |
| Mgi Id | MGI:7345962 | Doi | 10.4049/jimmunol.2200176 |
| Citation | Culberson EJ, et al. (2022) Monogenic TCRbeta Assembly and Expression Are Paramount for Uniform Antigen Receptor Specificity of Individual alphabeta T Lymphocytes. J Immunol 209(1):93-98 |
| abstractText | The ability of individual T and B cells to display Ag receptors of unique uniform specificity is the molecular basis of adaptive immunity. Most alphabeta T cells achieve uniform specificity by assembling in-frame genes on only one allelic copy of TCRbeta and TCRalpha loci, while others prevent incorporation of TCRalpha protein from both alleles into TCRs. Analysis of mice expressing TCR proteins from a restricted combination of transgenes showed that TCR protein pairing restrictions achieve uniform specificity of cells expressing two types of TCRbeta protein. However, whether this mechanism operates in the physiological context where each dual-TCRbeta cell expresses one set of a vast number of different TCRbeta proteins remains an open question, largely because there is a low, but significant, portion of cells carrying two in-frame TCRbeta genes. To resolve this issue, we inactivated one allelic copy of the TCRalpha locus in a new mouse strain that assembles two in-frame TCRbeta genes in an elevated fraction of cells. This genetic manipulation has no effect on the frequency of cells that display multiple types of alphabeta TCR, yet increases the representation of cells displaying TCRbeta proteins that generate more highly expressed TCRs. Our data demonstrate that some TCRbeta proteins exhibit differential functional pairing with TCRalpha proteins, but these restrictions have negligible contribution for ensuring uniform specificity of cells that express two types of TCRbeta protein. Therefore, we conclude that mechanisms governing monogenic assembly and expression of TCRbeta genes in individual cells are paramount for uniform specificity of alphabeta T lymphocytes. |
