Regulation by the H-2 gene complex of macrophage-lymphoid cell interactions in secondary antibody responses in vitro.

Abstract

The ability of antigen-bearing syngeneic and allogeneic peptone-induced peritoneal exudate macrophages to support development of primary and secondary antibody responses by murine lymphoid or spleen cells in vitro has been investigated. The antigen used was the terpolymer of L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT). Syngeneic and allogeneic macrophages supported development of comparable primary antibody responses to GAT, indicating that genetic restrictions do not limit efficient macrophage-lymphocyte interactions in primary responses. By contrast, immunized spleen or lymphoid cells developed secondary antibody responses preferentially when stimulated in vitro with GAT on macrophages syngeneic to the macrophages used to present GAT during in vivo immunization. Thus, genetic restrictions regulate efficient macrophage-lymphocyte interactions in secondary antibody responses. These restrictions have been demonstrated from 2 to 8 wk after a single immunization with limiting quantities of GAT and are controlled by the H-2 gene complex. The implications that immune lymphocytes selectively recognize and respond to antigen presented in the context of the macrophage membrane-antigen complex which sensitized the lymphocytes initially are considered.

Independent populations of primed F1 guinea pig T lymphocytes respond to antigen-pulsed parental peritoneal exudate cells.

“…If priming could be achieved with antigenpulsed allogeneic cells, then a subsequent restriction to responsiveness to antigen-pulsed cells of that allogeneic MHC type would be anticipated. Indeed, studies on the Tlymphocyte proliferative responses to trinitrophenylated PECs in guinea pigs, 2 on the in vitro antibody response to terpolymer ofglutamic acid, alanine, and tyrosine in mice (17), and on the transfer of delayed hypersensitivity to fowl gamma globulin in mice (18) are all consistent with this concept. Finally, one would anticipate that no MHC restriction in primary responses should exist, as the restriction would be a function of the initial priming regime.…”

The role of H-2-linked genes in helper T-cell function. VI. Expression of Ir genes by helper T cells.

“…There are a number of possible explanations for the expression of lr genes in helper T cells. Many experiments from this (7,(9)(10)(11) and other (8,15,16) laboratories have shown that/r-genes are expressed in B cells and Mth in a manner consistent with the idea that these genes control the recognition of B-cell-or Mth-bound antigen by T cells. By analogy, it may be, as suggested by Zinkernagel et al (17) and von Boehmer et al (5), that/r-genes, expressed in helper T cells, control the recognition of helper T-cell-bound antigen by a second T cell whose activity is required for the response of the helper T cell.…”

Purification and characterization of an L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT)-specific suppressor factor from genetic responder mice.

“…GAT (45,000 mol wt, Vega Biochemicals, Tucson, AZ) was prepared for use as antigen in culture (7), preparation of GAT-Md (8,9) and coupling to sheep erythrocytes (SRBC) for use as indicator cells in the hemolytic plaque assay (7), as described . Neonatal mice were injected with 2 X 10 6 syngeneic GAT-Mo for the induction of GAT-TSR, as previously described (6) .…”