Human T cells respond strongly to mouse major histocompatibility complex (MHC) antigens. The response is directed predominantly to the polymorphic determinants of the MHC antigens and there is little or no response to the nonpolymorphic determinants or to non-MHC antigens. Human cytotoxic T lymphocytes (CTL) are generated specific for the mouse class I MHC antigens and the CTL effectors are blocked by anti-Leu-2a antisera. Human interleukin 2-producing T cells are generated specific for mouse class II antigens and their induction is blocked by anti-Leu-3a antisera. These and other considerations lead us to propose a model for the T cell receptor that provides an explanation for several of the features of T cell recognition. In this model, the recognition of the "class" (I or II) of MHC antigen is separate from the recognition of the polymorphic determinants. We suggest that the initial recognition of the conserved "class" determinants positions another domain of the receptor so that it can only engage with the part of the MHC molecule carrying the polymorphic determinants.

"Background" or "spontaneous" plaque-forming cells (PFC) which arise during in vitro culture of mouse spleen cells may be eliminated by a hot thymidine pulse. This does not prevent the subsequent addition of sheep red blood cells (SRBC) or trinitrophenylated (TNP) SRBC eliciting a primary immune response.Using mouse spleen cells, resently primed by carrier (SRBC), it was found that an early "hot pulse" (for the first 2 4 hours of culture) can eliminate the anti-SRBC response, but not the primary anti-TNP response which is dependent o n carrier-specific, @-bearing, radioresistant spleen cells.

No abstract

Evidence is presented that indicates that two cells are required for the production of Con A-induced, helper T cell replacing factor. The factor production involves both a T cell and an IA,IE/C-positive non-T cell. The T cell and the Ia-positive cell need not be H-2 compatible. Limiting dilution analyses suggested that the Ia-positive cell is limiting in normal spleen. A hypothesis is put forward that the activation of T cells by Con A may involve "gluing" normally specific, functional T cells to the Ia expressing cells with which they would normally interact in antigen-specific activation.

The sites and modes of action of several B cell mitogens and interleukins were examined. Cell cycle analyses of B cell responses to several polyclonal activators including LPS, DXS, LPS plus DXS, and anti-immunoglobulin were performed. Two different states of B cell activation distinguished by RNA content, DNA content, and cell size were observed. LPS promoted transitions throughout the cell cycle, whereas DXS primarily caused exit from G0. Synergy between LPS and DXS was observed in elicitation of exit from G0. Activation by anti-immunoglobulin was found to be influenced by the antibody dose and the cell density of culture. Interleukins could influence anti-IgM-induced responses by increasing G0 exit, and by increasing commitment to DNA synthesis. A model of B cell activation in which cells are stimulated to a stage with intermediate RNA levels (G1A) by polyclonal activators is suggested. Some interleukins appear to be involved in this process. At G1A, cells are receptive to signals delivered by interleukins or some polyclonal activators that drive them to late G1 and DNA synthesis. After cell division, cells re-enter G1A in which interleukins or mitogens are necessary for a continued response.

No abstract

Two B cell growth factor activities have been previously described. One activity, present in the culture supernatants of PMA-induced EL4 is active in a co-stimulator assay with normal B cells and anti-immunoglobulin. The other activity is present in the culture supernatants of the alloreactive T cell line C.C3.11.75 and can be assayed in a co-stimulator assay with normal B cells and dextran sulfate or with BCL1 in vivo line B cell tumor. We have termed the first activity BCGFI and the second BCGFII. We have now shown that a very similar BCGFII activity can be obtained from EL4 culture supernatants induced by PMA. This (EL4)BCGFII has an apparent m.w. of 55,000, is eluted from DEAE Sephacel at 0.05 M NaCl, and has a pI of 5.5, which is clearly distinct from the properties of (EL4)BCGFI activity. (EL4)BCGFII activity is similar to but not identical to (DL)BCGFII. It differs from (DL)BCGFII in chromatographic behavior and in the kinetics of the response of BCL1 to the two factors. (EL4)BCGFII activity can be detected in 18 to 24 hr by virtue of its ability to cause in vitro proliferation of in vivo BCL1 tumor B cells.

No abstract