Antigen-specific soluble helper activity for murine major histocompatibility complex-encoded molecules. I. Kinetics of factor production after skin transplantation and genetic mapping of the H-2 region specificity.

Abstract

A basic, fundamental feature of an antigen-stimulated antibody response is the specificity of the binding capacity of the antibodies produced for determinants on that stimulating antigen. The exquisite specificity that is evidenced by antibodies for their antigenic determinants is also observed in T cell-mediated killing responses directed against cell surface antigenic molecules. The major target molecules for such cytotoxic T effector cells are associated with the major histocompatibility complex (MHC) 1, which is the H-2 complex in the mouse. Although "cross-reactive" killing of cellular targets obtained from mice with different H-2 haplotypes is frequently observed, recent evidence suggests that such cross-reactivity arises through the activation of distinct prekiller cell clones. Although the majority of the cell clones reactive to MHC antigens recognize the immunodominant specificity that is distinct for a given haplotype ("private" specificity), other distinct prekiller cell clones are specific for MHC determinants that are shared by a number of different H-2 haplotypes ("public" specificities) (1-4). Thus, the development of cytolytic effector T cells directed against cell surface H-2 antigenic determinants appears to follow the laws of clonal selection and immunological specificity. Similar rules concerning the generation of antigen-specific help for T cytolytic effector cell development have not been readily evident. T cell help for alloreactivity can be generated with virtually any H-2I-region

Xenogeneic antiserum to soluble products from activated lymphoid cells inhibits interleukin 1-mediated functions in the helper pathway of cytolytic-effector-cell differentiation.

“…We have described an antiserum that was raised in rats against skin graft-induced helper factor-containing supernatant (SgHFS) and have utilized this rat anti-SgHFS to examine the differentiation pathways of precytolytic effector T cells (11,22 …”

“…These antibodies are then used to further define the cell surface structure(s) involved in cell-cell collaboration as well as the function of various soluble factors involved in the differentiation of CTL. The contribution of a number of cell surface markers in both human and murine CTL activities as well as the lymphokine IL-2 have been studied using this approach (15-21).We have described an antiserum that was raised in rats against skin graft-induced helper factor-containing supernatant (SgHFS) and have utilized this rat anti-SgHFS to examine the differentiation pathways of precytolytic effector T cells (11,22 …”

“…IL-2, also called T-cell growth factor, supports the proliferative expansion of antigen-activated cells both in the helper T-cell pathway and in CTL differentiation (6,7). Other lymphokine/monokine factors besides IL-1 and IL-2 are required for the generation of CTL (4,5,(8)(9)(10)(11)(12)(13)(14). The role of IL-1 in the production of these other lymphokines/monokines has not been determined.…”