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Tcrb-V6+ T cells are deleted by an endogenous superantigen probably encoded by a mouse mammary tumor provirus (Mtv), Mtv-7, in association with major histocompatibility complex (MHC) class II molecules. In contrast, Tcrb-V6+CD4+ T cells are positively selected by MHC class II E molecules in Mtv-7- mice. We have examined the levels of Tcrb-V6+CD4+ and Tcrb-V6+CD8+ T cells from six combinations of backcross mice. In this paper we show that: 1) Tcrb-V6+CD8+ T cells can be positively selected by MHC class I molecules; 2) MHC class II A molecules can also influence the levels of Tcrb-V6+CD4+ T cells; 3) Mtv-7- NZW mice have a new Mtv, Mtv-44, which cosegregates with a gene encoding the partial deletion ligand for Tcrb-V6+ T cells; 4) the remaining Tcrb-V6+ T cells from mice with partial deletion of these T cells appear not to be anergized in the periphery.

Genes encoding endogenous superantigens causing Tcrb-V3+ T-cell deletion co-segregate with mouse mammary tumor proviruses (Mtv), Mtv-3, Mtv-6, and Mtv-13. In addition Mtv-1 has been implicated in deletion of these T cells. We have examined levels of Tcrb-V3+ T cells and Mtv integrations in the following offspring and their parental strains, [(CBA-T6 x NZW)F1 x CBA], [(CBA x C3H/He)F1 x CBA], and [(B10.S (9R) x NOD]F1 mice. We show that a new Mtv (Mtv-44) from NZW mice and Mtv-1 from C3H/He mice cosegregate with genes encoding ligands for partial deletion of Tcrb-V3+ T cells and that some NOD mice have an additional Mtv (Mtv-45) which is closely linked to Mtv-3.

Genes encoding superantigens which delete Tcrb-V3+ T cells co-segregate with mouse mammary tumor proviruses (Mtv), Mtv-1, Mtv-3, Mtv-6, Mtv-13, and Mtv-44. We have examined percentages of Tcrb-V3+ T cells and Mtv integrations in [(B10 x NZB)F1 x B10.BR] mice, and show that Mtv-27 as well as Mtv-3 from NZB mice co-segregate with genes encoding deletion ligands for Tcrb-V3+ T cells without recombination.

Tcrb-V-specific positive and negative selection of T cells has been well documented. In contrast, nothing is known about Tcra-V-specific selection. Using Tcra-V8-specific KT50 antibody Tcra-V8-specific selection of T cells has been examined. The CD8+ T cell subpopulation bearing Tcra-V8 are shown to be negatively selected by major histocompatibility complex (MHC) class I H-2Kd and H-2Dd/Ld molecules. Furthermore, percentages of these T cells are also influenced by Tcra-V haplotypes. Involvement of non-H-2 self (super)antigens in this MHC class I restricted negative selection, however, remains to be determined.

The Tcrb-V10b+ T cell population has been examined with a newly established antibody, KT10b, specific for Tcrb-V10b but not Tcrb-V10a. H-2E+ mice have higher levels of Tcrb-V10b+ T cells (4.3%-11.0%) than H-2E- mice (2.2%-4.9%). This difference appears to be determined by levels of Tcrb-V10b+ T cells in the CD4 population. F1 hybrid mice between H-2E+ and H-2E- mice dominantly express higher levels of Tcrb-V10b+ T cells. [NOD (E-) x (NOD x A (E+))F1] backcross mice show positive selection of Tcrb-V10b+CD4+ T cells by H-2E. On the other hand other backcross analyses reveal positive selection of Tcrb- V10B+CD8+ T cells by certain major histocompatibility class I molecules. Involvement of non-H-2 antigens in these positive selections remains to be determined.

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.

A gene encoding the endogenous superantigen Mlsc, which deletes Tcrb-V3+ T cells in the NOD inbred mouse strain, was found to co-segregate with Mtv-3 on chromosome 11. This identifies a fourth gene encoding a deletion ligand for Tcrb-V3+ T cells and extends recently published observations in support of the hypothesis that a number of endogenous superantigens are the products of Mtv proviruses.

The V beta 4+ T-cell population was examined with a newly established antibody, KT4, specific for V beta 4. Between 4.8% and 19.4% of CD3+ peripheral T cells from various inbred strains of mice or F1 hybrids expressed V beta 4. The CD4 T-cell population had higher numbers of V beta 4+ T cells (5.5%-20.6%) than the CD8 T-cell population (2.5%-10.7%). Deletion of certain V beta-expressing T cells due to the presence of the Mlsa antigen and/or the absence of certain Tcrb-V genes increased relative numbers of V beta 4+ T cells. The data suggest that V beta 4+ CD8+ T cells might be positively selected by H-2d molecules.

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.