The T-cell receptor (TCR) repertoire is selected in the thymus after rearrangement of genes encoding TCR alpha and beta chains. 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, 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; 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; V beta 3 T cells by Mls-2a and Mls-3a; V beta 11 T cells by ligands encoded by independently segregating genes; and V beta 5 T cells by ligands encoded by two genes. Chromosome 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 and that a ligand gene for V beta 11 deletion is linked to the CD8 locus on chromosome 6. 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.(ABSTRACT TRUNCATED AT 250 WORDS)

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The sexual phenotype of an adult mammal depends on whether the fetal gonad has differentiated as a testis or as an ovary. Because individuals of XY or XXY sex chromosome constitution develop as males, while XX and XO individuals develop as females, the presence of a Y chromosome seems normally to be required for testis differentiation and its absence to be necessary for differentiation of an ovary. The nature of the hypothetical Y-dependent substance responsible for masculinization of the indifferent gonad has been a matter for debate. A male-specific transplantation antigen, H-Y, has been known for many years and more recently a serologically detected antigen, also male-specific, has been reported. Those who believe that the two are antigenically distinct refer to the latter as SDM (serologically detected male) antigen, but many refer to both as H-Y antigen. The hypothesis that H-Y is itself the Y-dependent testis inducer, although supported by little or no direct evidence, is economical and hence attractive. H-Y antigen is frequently stated to be the substance responsible for primary sex determination (for example, see ref. 11). We report here that H-Y is absent from certain mice that develop testes and are of indisputably male phenotype, hence this transplantation antigen is unlikely to be responsible for testis determination.

Two monoclonal antibodies specific for the mouse T-cell receptor (Tcr) have been established by immunization with a V beta 11+ T-cell clone, clone C6. One is a rat antibody, KT11 (IgG2b, k), specific for the V beta chain of C6, V beta 11. This was demonstrated by the fact that the strain distribution pattern of KT11+ cells was similar to that of V beta 5, 8, 9, 11, 12, and 13 and that the gene that encodes the molecule detected by KT11 was closely linked to V beta 8 in (B10 X SJL)F1 X SJL backcross mice. Furthermore, V beta of C6 has been cloned from a lambda gt10 cDNA library and was demonstrated to be identical to the V beta 11 published sequences. All strains of mice that do not express major histocompatibility complex class II E molecules had higher numbers of KT11+ cells than E+ strains. The KT11+ population in A strain mice and its H-2 congenic strains, however, was not affected by the presence or absence of E molecules. The other is a mouse antibody, KTL2 (IgM), specific for the idiotope of the Tcr expressed on the clone C6. Both antibodies were mitogenic and induced cytotoxicity. Expression of epitopes detected by KT11 or KTL2 was down-modulated by a T3 epsilon-specific antibody 145-2C11.

In mice, V beta-specific negative selection is mediated by a number of superantigens encoded by various mouse mammary tumor viruses. We have identified Mtv-3, Mtv-27, Mtv-44, Mtv-8, Mtv-9, Mtv-11, and MMTV(D2.GD), and have confirmed Mtv-1. Although specificities of superantigens correlate well with sequences of their carboxy terminal regions, Mtv-44 appears to be an exception: the product is specific for V beta 3, V beta 6, V beta 8.1, and V beta 9. It remains to be determined whether Mtv-44 produces one or two different superantigens to exhibit this specificity. V beta 5+ T-cell deletion is induced by two groups of superantigens: V beta 3-specific superantigens encoded by Mtv-1, Mtv-3, Mtv-6, Mtv-13, Mtv-27, and Mtv-44, and V beta 11-specific superantigens encoded by Mtv-8, Mtv-9, and Mtv-11. Furthermore, these V beta 3-specific superantigens are also specific for V beta 17a(cz). In contrast, V beta-specific positive selection and V alpha-specific positive and negative selection do not seem to involve non-H-2 (super)antigens, although their involvement can not be excluded. In the near future, superantigens, powerful modulators of T-cell functions, will be exploited for clinical applications.