A Human Minor Histocompatibility Antigen Specific for B Cell Acute Lymphoblastic Leukemia

Human minor histocompatibility antigens (mHags) play an important role in the induction of cytotoxic T lymphocyte (CTL) reactivity against leukemia after human histocompatibility leukocyte antigen (HLA)-identical allogeneic bone marrow transplantation (BMT). As most mHags are not leukemia specific but are also expressed by normal tissues, antileukemia reactivity is often associated with life-threatening graft-versus-host disease (GVHD). Here, we describe a novel mHag, HB-1, that elicits donor-derived CTL reactivity in a B cell acute lymphoblastic leukemia (B-ALL) patient treated by HLA-matched BMT. We identified the gene encoding the antigenic peptide recognized by HB-1–specific CTLs. Interestingly, expression of the HB-1 gene was only observed in B-ALL cells and Epstein-Barr virus–transformed B cells. The HB-1 gene–encoded peptide EEKRGSLHVW is recognized by the CTL in association with HLA-B44. Further analysis reveals that a polymorphism in the HB-1 gene generates a single amino acid exchange from His to Tyr at position 8 within this peptide. This amino acid substitution is critical for recognition by HB-1–specific CTLs. The restricted expression of the polymorphic HB-1 Ag by B-ALL cells and the ability to generate HB-1–specific CTLs in vitro using peptide-loaded dendritic cells offer novel opportunities to specifically target the immune system against B-ALL without the risk of evoking GVHD

Type-1 and type-2 CD8+ T-cell subsets isolated from chronic adult periodontitis tissue differ in surface phenotype and biological functions.

Cloning of CD8+ T cells expressing the alpha beta T-cell receptor from inflamed human gingiva revealed that at least two different subsets were found within the tissue and that these subsets were able to interact with each other. One subset produced high levels of interferon-gamma (IFN-gamma) and no interleukin-4 (IL-4) or IL-5, exhibited phytohaemagglutinin (PHA)- or anti-CD3-mediated cytolytic activity, and were CD28+. The other subset produced high levels of IL-4 in combination with IL-5, displayed no cytotoxicity and were CD28-. From the latter subset CD8+ T-cell clones were able to suppress the proliferative response of cytotoxic CD8+ T-cell clones. This suppression could be abolished by anti-IL-4 monoclonal antibodies. However, IL-4 alone was not able to induce the suppression. Our results indicate that CD8+ T cells might participate in local immune responses by the suppression of IFN-gamma-producing cells and by favouring humoral responses via the production of IL-4 and IL-5

Cloning, characterization, and antigen specificity of T-lymphocyte subsets extracted from gingival tissue of chronic adult periodontitis patients.

Chronic periodontitis is characterized by dense infiltrations of B and T lymphocytes within the gingival connective tissue. Distinct anaerobic gram-negative bacteria as well as autoimmunity to collagen have been reported to play a role in the etiology and the pathogenesis of this disease. Here we describe the cloning and characterization of CD4+ and CD8+ T lymphocytes isolated from inflamed gingival tissue obtained from four patients with chronic periodontitis. Clones were raised with phytohemagglutinin and interleukin-2 and tested for proliferation in response to whole-cell antigens of Porphyromonas gingivalis, Prevotella intermedia, Actinobacillus actinomycetemcomitans, human collagen type I, and two bacterial heat shock proteins. CD4+ T-cell clones reactive with collagen type I were obtained from all four patients. Eighty percent of these clones had phenotypes resembling the mouse type 2 T helper (Th) phenotype, i.e., they produced high levels of interleukin-4 and low levels of gamma interferon. No collagen-type-I-reactive CD8+ clones were obtained. Bacterial-antigen-reactive CD4+ and/or CD8+ T-cell clones were also obtained from each patient, and the majority of the clones showed a Th0-like cytokine pattern and produced equal amounts of interleukin-4 and gamma interferon. Although most clones were reactive with P. intermedia, it seems that the immune response is not strictly directed against this particular microorganism, as clones reactive with one of the other bacteria were also obtained from two patients. We propose that collagen-specific CD4+ Th2-like T cells contribute to the chronicity of periodontitis but that their modes of activation might be controlled by Th0-like T cells specific for periodontitis-associated bacteria