Insulin‐specific T cell help to TNP‐specific B cells requires activation via the antigen T cell receptor

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Abstract
In the present study, the production of large numbers of insulin (Ins)‐specific, H‐2‐ restricted T helper (Th) cell clones is described. Among 148 clones analyzed, 121 clones had Th cell function, and these were divided into 75 Ins‐specific Th cell clones and 52 autoreactive clones. The 148 clones were isolated from Ins‐specific T cell lines produced by in vitro stimulation of T lymphocytes from (b ± d)F1 mice immunized with Ins 7, 14, 32 or 56 days before. The following characteristics were tested with regard to the Th, cell clones: restriction specificity and antigen requirement for optimal help or interleukin 2 (IL2) production. No differences in these characteristics were found among clones originating from day 7, 14, 32 or 56 T cell lines. A preference for H‐2b as restriction element and an antigen concentration of about 0.01 μg trinitrophenylated (TNP)‐Ins/ml for optimal help were general traits. Optimal IL2 release is not yet obtained with 100 ug TNP‐Ins/ml. Thus, the antigen requirement for optimal help and IL 2 release differs by a factor 104 at least. Certain twice‐cloned Th cell lines were tested for IL2 production when stimulated with anti‐Thy‐1 monoclonal antibodies (mAb). All clones analyzed were stimulated by mAb H155 but not with mAb H140 nor with mAb against Lyt‐1, L3T4, LFA‐1 or H‐2K/D molecules. Therefore, we determined whether TNP‐conjugated H155 mAb would mediate Th cell‐B cell collaboration as well as TNP‐Ins. The results with nine different Th cell clones and six different TNP‐conjugated mAb used in a 107‐fold concentration range showed that Th cell clones have to be triggered via the T cell receptor for expression of helper function to B cells. Thus, though IL2 gene activation, synthesis or release apparently can be activated via at least two pathways: (a) T cell receptor or (b) Thy‐1, it seems that activation of the genes responsible for synthesis and release of the helper factors, which ensure antigen‐specific B cell proliferation and differentiation, needs Th cell‐B cell contact mediated via the antigen‐specific T cell receptor.