Mouse alloantibodies capable of blocking cytotoxic T-cell function. I. Relationship between the antigen reactive with blocking antibodies and the Lyt-2 locus.

Abstract

In an attempt to produce allonatibodies to cytotoxic T-cell receptors, hyperimmune anti-lymphocyte antisera have been raised in mice of various strain combinations, and have been tested for their ability to block allogeneic cell-mediated lymphocytotoxicity (CML) in the absence of complement at the T killer cell level. Most of the sera failed to show any significant and reproducible inhibitory effects. However, among C3H anti-B10.BR antisera, some sera were found to be capable of significantly inhibiting CML. This effect was attributable to antibodies reacting with the killer population rather than the target cells, because the sera inhibited B10 anti-C3H CML but not C3H anti-b10 CML. Among mouse strains tested, A/J, BALB/c, B10, and B6 strains were sensitive to the inhibitory effect of the sera whereas AKR, CBA, C3H, and DBA/2 strains were insensitive. The sensitivity of killer cells to the inhibitory effect correlated well with the strain distribution of the Lyt-2.2 antigen. In the presence of complement, these same sera were toxic to 100% of spleen cells of AKR, BALB/c, B10, and DBA/2 strains, with comparable cytotoxic titers. Thus, the inhibitory activity of the sera could not be explained by nonspecific effects of high-titered antibodies. To study the relationship between the antigen(s) responsible for the blocking effect and Lyt-2-linked genes, killer cells from Lyt-2 congenic strains were tested and conventional anti-Lyt-2.2 antisera were raised in an appropriate congenic strain combination. Killer cells from B6, but not from B6.Ly2.1 animals, were significantly sensitive to the blocking effects of the inhibitory C3H anti-B10.BR sera. The conventional anti-Lyt.2.2 sera did produce CML blocking, although there was no apparent correlation between such blocking and the anti-Lyt-2.2 cytotoxic titer. These results thus indicate that the target molecules responsible for blocking of killer cells are encoded or regulated by genes that are closely linked to or identical with Lyt-2.

Anti-CD8 Antibodies Can Trigger CD8+ T Cell Effector Function in the Absence of TCR Engagement and Improve Peptide–MHCI Tetramer Staining

“…Anti-CD8 Abs have been used widely to investigate the role of CD8 in CD8 + T cell activation. Early studies showed that preincubation with anti-CD8 Abs can block conjugate formation between effector and target cells (16) and inhibit CD8 + T cell activation in response to cognate pMHCI presented on the target cell surface (17)(18)(19)(20). These findings provided key evidence that CD8 was important in the process of CD8 + T cell activation.…”

“…Anti-CD8 Abs are integral to the flow cytometric detection of pMHCI-restricted T cells and have been used extensively in the past to identify an important role for CD8 in CD8 + T cell activation (16)(17)(18)20). Most studies have concluded that anti-CD8 Abs inhibit the recognition of cognate Ag (19,21,22).…”

Hypothesis: The MHC-restricted T-cell receptor as a structure with two multistate allosteric combining sites

“…Moreover, the specificity of the enzyme for the four different substrates (CDP, UDP, GDP and ADP) depends, in a parametric fashion, on the nature of effector ligands. Recent studies have shown that the Ly2 and UT4 molecules playa role in antigen recognition by T cells (Nakayama et al, 1979;Shinohara and Sachs, 1979;Swain et al, 1984). In the case of the Ly2 molecule, available data suggest that this molecule enhances the affinity of antigen binding, being essential when the T-cell receptor has a borderline affinity for antigen, but -not when the receptor has an intrinsically high affinity.…”

PPD‐Specific Proliferative Response in Humans: I. Analysis of PPD‐Specific Proliferative Cells from Tuberculous Pleurisy Patients and Healthy Controls with Monoclonal Antibodies Specific for Human T Subsets

“…Because of their selective expression on functionally distinct subpopulations, the macromolecule(s) carrying the Lyt-2 and Lyt-3 antigens have been thought to perform essential functions, most likely involving cellular interactions or recognition of antigen. Support for this idea has come from functional studies of cytotoxic effector T cells, in which antibodies to Lyt-2 or Lyt-3 were shown to block killing by binding to the effector cells (12,17). Ledbetter et al have reported the biochemical properties and cell surface distribution of T lymphocyte subpopulations of the homologue of Lyt 1, 2 and 3 antigens and Leu 1 and Leu 2 antigens, but the homologue of Leu 3 antigen in mice has not been identified (10).…”