GENES ENCODING LIGANDS FOR DELETION OF V-BETA-11 T-CELLS COSEGREGATE WITH MAMMARY-TUMOR VIRUS GENOMES

THE T-cell receptor (TCR) repertoire is selected in the thymus after rearrangement of genes encoding TCR alpha and beta chains 1. Selection is based on the recognition by newly emergent T cells of self-ligands associated with molecules of the major histocompatibility complex: some combinations result in positive selection, others in negative selection. Negative selection, or clonal deletion, is an important mechanism for eliminating autoreactive T cells. A group of self-ligands involved in clonal deletion was identified because they, like exogenous superantigens 2, were recognized by almost all T cells expressing particular TCR V-beta genes. V-beta-17a T cells are deleted by a tissue-specific ligand 3,4; V-beta-6, V-beta-7, V-beta-8.1 and V-beta-9 T cells are deleted by the minor lymphocyte-stimulating (Mls) determinant Mls-1a (refs 5-8); V-beta-3 T cells by Mls-2a and Mls-3a (refs 9,10); V-beta-11 T cells 11 by ligands encoded by independently segregating genes; and V-beta-5 T cells by ligands encoded by two genes 12. Chromosomes mapping using recombinant inbred strains of mice and classic backcrosses show that Mls-1a in DBA/2 mice is encoded on chromosome 1, that one of the two ligand genes for deletion of V-beta-5 T cells maps to chromosome 12 (ref. 12) and that a ligand gene for V-beta-11 deletion is linked to the CD8 locus on chromosome 6 (ref. 11). Here we present evidence from three sets of backcross mice for concordance between V-beta-11 deletion ligand genes on chromosomes 6, 12 and 14 and endogenous mouse mammary tumour virus integrant (Mtv) genomes. Our results indicate that the V-beta-11 deletion ligands are products of Mtv genomes.