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Evidence that Mls-2 antigens which delete V beta 3+ T cells are controlled by multiple genes
A M Pullen1, P Marrack, J W Kappler
1Howard Hughes Medical Institute, National Jewish Center, Denver, CO.
Abstract:
V beta 3+ T cells are eliminated in Mls-2a mice carrying some, but not all, H-2 types. Analysis of AKXD and BXD recombinant inbred strains showed that Mls-2a (formerly Mlsc) was not the product of a single gene and suggested that at least two non-H-2 genes control V beta 3 levels. Studies of the progeny of a B10.BR x (C3H/HeJ x B10.BR)F1 backcross confirmed the existence of two V beta 3+ T cell deleting genes: one unlinked and one linked to Ly-7, which we propose be called Mls-2 and Mls-3, respectively. Mls-2a induces partial deletion of V beta 3+ T cells with a bias toward deleting CD4+ cells. It stimulates V beta 3+ hybrids and may be linked to Mtv-13 on chromosome 4. A third non-H-2 gene is implicated in enhancing the presentation of Mls-2a. Mls-3a causes elimination of all V beta 3+ T cells in H-2k and H-2d mice but poorly stimulates V beta 3+ hybrids.
Insights
Two non-H-2 genes, Mls-2 and Mls-3, control the elimination of V beta 3+ T cells in mice. These genes influence T cell receptor V beta usage and immune tolerance.
Area of Science:
- Immunology
- Genetics
- T cell biology
Background:
- T cells expressing specific T cell receptor (TCR) V beta elements can be deleted in mice based on their H-2 type.
- Previous studies suggested a single gene, Mls-2a, controlled V beta 3+ T cell deletion, but its genetic basis was unclear.
Purpose of the Study:
- To elucidate the genetic control of V beta 3+ T cell elimination in Mls-2a mice.
- To identify and map the genes responsible for T cell deletion.
Main Methods:
- Analysis of recombinant inbred strains (AKXD and BXD).
- Backcross analysis of B10.BR x (C3H/HeJ x B10.BR)F1 progeny.
- Genetic mapping of deletion genes.
Main Results:
- Identified two non-H-2 genes controlling V beta 3+ T cell levels, named Mls-2 and Mls-3.
- Mls-2 is unlinked to H-2 and causes partial deletion of V beta 3+ T cells, with a bias towards CD4+ cells.
- Mls-3 is linked to Ly-7 and mediates complete elimination of V beta 3+ T cells in specific H-2 contexts (H-2k, H-2d).
- A third gene enhances Mls-2a presentation, and Mls-2 may be linked to Mtv-13 on chromosome 4.
Conclusions:
- V beta 3+ T cell deletion is controlled by at least two distinct genes, Mls-2 and Mls-3.
- These genes exhibit differential effects on T cell populations and H-2 restriction.
- Further characterization of Mls-2 and Mls-3 provides insights into immune tolerance mechanisms.