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The genetic basis of negative selection of Tcrb-V11+ T cells
1Transplantation Biology Section, MRC Clinical Research Centre, Middlesex, England.
Abstract:
Non-H-2 genes responsible for negative selection of Tcrb-V11+ T cells were examined using backcross mice of various strains with C58, which does not delete Tcrb-V11+ T cells. Two independently segregating genes were found: one leading to partial deletion was closely linked to Ly-2/Ly-3 on chromosome 6, and the second giving virtually complete deletion has not yet been mapped. The A strain had only the former, whereas BALB/c, BALB.K, B10.BR, CBA-T6, C3H/He, and DBA/2 expressed both of these genes. Although a gene(s) of the NIH strain led only to partial deletion, the chromosomal localization of the gene(s) has not yet been determined: no informative polymorphic molecules are expressed from genes on chromosome 6 of this strain.
Insights
Researchers identified two non-H-2 genes controlling T-cell receptor beta (Tcrb)-V11+ T cell deletion. One gene, linked to chromosome 6, causes partial deletion, while another causes near-complete deletion.
Area of Science:
- Immunology
- Genetics
Background:
- Negative selection is crucial for T cell repertoire development.
- Tcrb-V11+ T cells are subject to deletion by specific non-H-2 genes.
Purpose of the Study:
- To identify and map non-H-2 genes responsible for the negative selection of Tcrb-V11+ T cells.
Main Methods:
- Utilized backcross mice from various strains crossed with C58 mice (which lack Tcrb-V11+ T cell deletion).
- Analyzed segregation patterns of deletion phenotypes.
Main Results:
- Identified two independently segregating non-H-2 genes involved in Tcrb-V11+ T cell deletion.
- One gene, partially responsible for deletion, is closely linked to Ly-2/Ly-3 on chromosome 6.
- A second gene, responsible for virtually complete deletion, remains unmapped.
- Different mouse strains (A, BALB/c, BALB.K, B10.BR, CBA-T6, C3H/He, DBA/2, NIH) exhibit varying combinations of these deletion genes.
Conclusions:
- Non-H-2 genes play a significant role in the negative selection of Tcrb-V11+ T cells.
- Genetic mapping has localized one deletion gene to chromosome 6, while another remains unmapped, highlighting genetic diversity in T cell selection.