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Hybrid resistance (HR) to parental bone marrow growth is specifically directed against hemopoietic histocompatibility (Hh-1) Ag that are present in parental bone marrow cells (bmc). The mechanism of HR seems to be a multistep process. According to a model we proposed earlier, a T cell recognizes the Hh-1 Ag and stimulates a macrophage to secrete IFN-alpha/beta (recognition phase). IFN-alpha/beta activates a NK-like cell that specifically kills the parental bmc (effector phase). We have also described in a previous paper that serum from resistant F1 hybrids contains a humoral factor that seems to be involved in the effector phase of HR. In the present work, we study the role and the nature of this humoral factor. Our results show that this humoral factor: 1) is present in all resistant H-2Db heterozygous F1 hybrids we have tested but not in nonresistant H-2Db homozygous mice; 2) seems to recognize the Hh-1b Ag because it is absorbed on bmc from Hh-1b mice but not on bmc from Hh-1d and Hh-1- mice; and 3) is an IgG1 Ig (natural antibody). These results could help us to explain the specificity of HR at the effector phase by supposing that this natural antibody recognize the Hh-1 Ag and enable NK-like cells to kill parental bmc cells in Hh-1 specific manner.

T lymphocyte responses to a protein Ag are restricted to a limited number of determinants and not to all peptides capable of binding to MHC class II molecules. This focusing of the immune response is defined as immunodominance and has been observed with numerous protein Ags. In the H-2d haplotype, hen egg-white lysozyme (HEL)-specific T lymphocytes react with I-Ed-restricted peptides derived from a single immunodominant (ID) region (HEL 103-117). Moreover, we have recently found that another region of HEL (HEL 7-31) binds to I-Ad molecules and is efficiently processed and presented by splenocytes. HEL7-31 is as tolerogenic as the ID region in HEL transgenic mice. The present report demonstrates that the subdominance of the HEL 7-31 region is not due to a defect in the T cell repertoire, since specific TCRs can be found in all BALB/c mice. We show that normal and lymphoma B cells present efficiently HEL regions 103-117 and 7-31, whereas dendritic cells favor the ID region only. These results suggest that dendritic cells play a major role in the focusing of the immune response against a few antigenic determinants, while B lymphocytes may diversify the T cell response by presenting a more heterogeneous set of peptide-MHC complexes.

We have analyzed the reactivity of a mouse monoclonal antibody directed against the human T cell receptor for antigen (TCR). This antibody (111-427) of immunoglobulin G1 isotype has been produced in a BALB/c mouse immunized with HPB-ALL cells and normal human peripheral blood leukocytes. It reacts specifically with the HPB-ALL lymphoma and 2 to 7% of normal human blood lymphocytes, on which it has a mitogenic effect in vitro. We have shown that it immunoprecipitates the αβ TCR of HPB-ALL and that it is specific for the Vβ5.3 chain of the human TCR. In addition, we have observed that this antibody stains a minor fraction of T lymphocytes in different strains of mice. We have screened a number of murine T cell clones or hybridomas and have found that the T cell hybrid line D0.11.10.S4.4 is positive. We have been unable to immunoprecipitate reproducibly the molecule recognized by 111-427 after 125I cell surface labeling and cell lysis in NP-40 or digitonin, probably because of low-affinity binding. On Western blotting, 111-427 revealed one band that has an apparent molecular mass of 89 kDa in nonreducing conditions and disappears after reduction. Similar results were obtained in parallel with the F23.1 and F23.2 antibodies. Thus, this antibody appears to recognize an epitope present primarily on the Vβ8.2 chain of the mouse TCR. We have assayed its capacity to stimulate splenic T lymphocytes in vitro. We have observed that it is capable of triggering, to a minor degree in soluble form and very effectively when coupled to Sepharose beads, the proliferation of spleen T lymphocytes from mice chronically infected with the blood parasite Trypanosoma cruzi. J. Leukoc. Biol. 57: 491–499; 1995.

Hybrid resistance (HR) to parental bone marrow growth is specifically directed against hemopoietic histocompatibility (Hh-1) Ag that are present in parental bone marrow cells (bmc). The mechanism of HR seems to be a multistep process. According to a model we proposed earlier, a T cell recognizes the Hh-1 Ag and stimulates a macrophage to secrete IFN-alpha/beta (recognition phase). IFN-alpha/beta activates a NK-like cell that specifically kills the parental bmc (effector phase). We have also described in a previous paper that serum from resistant F1 hybrids contains a humoral factor that seems to be involved in the effector phase of HR. In the present work, we study the role and the nature of this humoral factor. Our results show that this humoral factor: 1) is present in all resistant H-2Db heterozygous F1 hybrids we have tested but not in nonresistant H-2Db homozygous mice; 2) seems to recognize the Hh-1b Ag because it is absorbed on bmc from Hh-1b mice but not on bmc from Hh-1d and Hh-1- mice; and 3) is an IgG1 Ig (natural antibody). These results could help us to explain the specificity of HR at the effector phase by supposing that this natural antibody recognize the Hh-1 Ag and enable NK-like cells to kill parental bmc cells in Hh-1 specific manner.