Distinct Ir genes for helper and killer cells in the cytotoxic response to H-Y antigen.

Abstract

The H-Y-specific cytotoxic T-cell response requires helper cells: cells from bone marrow chimeras B6 X CBA leads to B6, B6 X CBA leads to B10.A (5R), or B6 X CBA leads to CBA are each unable to respond to H-2k male cells. If, however, cells from B6 X CBA leads to B6 or B6 X CBA leads to B10.A (5R) chimeras are adoptively transferred together with cells from B6 X CBA leads to CBA chimeras, H-Y-specific CTL restricted to H-2k can be obtained. Thus, cells from B6 X CBA leads to B6 or B6 X CBA leads to B10.,A (5R) chimeras (restricted to the left end of the H-2b haplotype) can help CTL precursors from B6 X CBA leads to CBA chimeras (restricted to H-2k). The two classes of T cells required for the CTL response to H-Y antigen are controlled by different IR genes. All H-Y-specific CTL obtained from chimeras B6 + CBA leads to B6 X CBA were found to be of B6 origin. This suggests that CTL or their precursors must express antigens encoded in the left end of the H-2b haplotype for interaction with helper cells.

Development of a lipopeptide-based therapeutic vaccine to treat chronic HBV infection. I. Induction of a primary cytotoxic T lymphocyte response in humans.

“…Theradigm-HBV or placebo was administered by injecting 0.5 ml s.c. into the upper forearm. Subjects receiving Theradigm-HBV were boosted with an identical dose to that used for priming [28][29][30][31][32][33][34][35] To determine the CTL responses in immunized subjects, 3-4 x 106 PBMC collected at various pre-and postvaccination timepoints were stimulated in vitro with 10 ag/ml Statistical methods. To determine the relationship between dose of Theradigm-HBV injected and CTL response induced, a linear-regression model was fit between the logo of the dose injected and the loglo of the response obtained.…”

Helper T cells for cytotoxic T lymphocytes need not be I region restricted

“…Experiments interpreted as supporting the role of I region-recognition events during the process of CTL induction include (a) studies demonstrating the augmentation of CTL responses to foreign H-2K and D antigens by I region-reactive T cells (5,6), (b) studies of CTL responses to viral (2) or non-H-2 cell surface antigens (7) or hapten (8), demonstrating an influence of I region genes expressed by cells of the thymus on the response phenotype of T cells that mature therein, (c) a study demonstrating the apparent depletion, by in vivo negative selection procedures, of I region-restricted helper cells required for an in vitro secondary CTL response specific for minor histocompatibility antigens (9), and (d) the finding that Ia + non-T accessory cells are required for in vitro CTL responses (4, 10, 1 1). In addition, studies of the Ir gene defect ofnonresponder strains in the CTL response of female mice to the male antigen, H-Y, have been interpreted in terms of I region-restricted helper T cells (1,7,(12)(13)(14)(15).…”

“…Nonetheless, on the basis of mostly indirect results from a variety of experimental approaches, the most prevalent model of CTL activation is one that closely parallels models of B cell activation, i.e., that I regionrestricted helper T cells activated by interaction with antigen in the context of I region determinants deliver inducing signals to antigen-activated precursor CTL (1)(2)(3)(4)(5). In some models, the helper T cell interacts with CTL precursors via the restricted recognition of I region determinants expressed by the CTL precursor (1,2).…”

“…Nonetheless, on the basis of mostly indirect results from a variety of experimental approaches, the most prevalent model of CTL activation is one that closely parallels models of B cell activation, i.e., that I regionrestricted helper T cells activated by interaction with antigen in the context of I region determinants deliver inducing signals to antigen-activated precursor CTL (1)(2)(3)(4)(5). In some models, the helper T cell interacts with CTL precursors via the restricted recognition of I region determinants expressed by the CTL precursor (1,2). Experiments interpreted as supporting the role of I region-recognition events during the process of CTL induction include (a) studies demonstrating the augmentation of CTL responses to foreign H-2K and D antigens by I region-reactive T cells (5,6), (b) studies of CTL responses to viral (2) or non-H-2 cell surface antigens (7) or hapten (8), demonstrating an influence of I region genes expressed by cells of the thymus on the response phenotype of T cells that mature therein, (c) a study demonstrating the apparent depletion, by in vivo negative selection procedures, of I region-restricted helper cells required for an in vitro secondary CTL response specific for minor histocompatibility antigens (9), and (d) the finding that Ia + non-T accessory cells are required for in vitro CTL responses (4, 10, 1 1).…”

The generation and activation of memory class I MHC restricted cytotoxic T cell responses to influenza A virus in vivo do not require CD4+ T cells

“…For in vitro secondary (memory) Tc cell responses, such a requirement has been deduced from a variety of experimental approaches such as limiting dilution analysis (8). antibody blocking (9).cell depletion (10)(11)(12)and genetic manipulations (13,14). However, CD4+ T cells are not found to be required for in vivo primary Tc cell responses against ectromelia virus (5).…”