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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.

Two monoclonal antibodies, KT50 and KT65, specific for V alpha 8 have been established. This was determined as follows: (a) 4 T cell clones, C6, R1, G22 and I9, out of 43 T cell clones with various antigen specificities, major histocompatibility complex restrictions and V beta usages not only bound KT50 and KT65 but also expressed V alpha 8 mRNA, (b) KT50 and KT65 precipitated molecules from the clone C6 similar to the T cell receptor molecules precipitated in C6 cells by KT11 (anti-V beta 11) or KTL2 (anti-Ti) and (c) KT50 and KT65 were mitogenic and induced cytotoxicity. All strains of mice so far examined have populations of KT50+ and KT65+ T cells of 1.4%-3.6% and 0.9%-2.6%, respectively. Different H-2 haplotypes were not observed to affect the number of cells expressing KT50 or KT65. In addition KT15 (anti-CD8), without cross-linking to KT50 or KT65, augmented proliferation triggered by KT50 or KT65.

Antigen-specific unresponsiveness lasting at least 2 weeks can be induced in a T cell clone by 24-h pretreatment with mitogenic anti-T cell receptor antibodies. In this report the relationship is explored between the antigen-specific unresponsiveness and activation pathways triggered via the T cell receptor and Thy-1: the latter pathway is dependent on the former. A mitogenic anti-Thy-1 antibody (KT16) made the T cell clone unresponsive to specific antigen and to an anti-T cell receptor antibody coupled to Sepharose. The unresponsiveness lasted for at least 7 days. However, cells made unresponsive to specific antigen in these ways (the T cell receptor and Thy-1) could be activated by both interleukin 2 and KT16. KT16 down-modulated the T cell receptor immediately after the pretreatment, but not on day 7 after the pretreatment. These facts indicate that the state of the unresponsiveness was caused by blocking transduction of an activation signal triggered by the T cell receptor to an activation pathway shared by the T cell receptor and Thy-1.

Three monoclonal antibodies (1G3, 2H11, and 3G12) specific for a syngeneic Ek-specific T-cell clone, clone 4, have been established. The antibodies specifically blocked not only the activation of the clone in response to the specific antigen Ek but also the activation by IL-2. Kinetic studies of the blocking activity revealed that the antibodies blocked activation not only through steric hindrance of the antigen-binding site of the receptor but also via inhibition of DNA synthesis. The antibodies induced unresponsiveness of the clone to the specific antigen Ek, but not to nonspecific activation by IL-2. The state of unresponsiveness induced by 1G3 continued for 14 days, the longest time so far examined. The recovery from the unresponsiveness (tolerance) was not observed unless the clone cells proliferated vigorously in response to IL-2. The idiotope recognised by 1G3 was different from that by 2H11 and/or 3G12. This might explain some functional differences elicited by the antibodies.

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.