       Document 0237
 DOCN  M9620237
 TI    Oxidative/reductive conjugation of mannan to antigen selects for T1 or
       T2 immune responses.
 DT    9602
 AU    Apostolopoulos V; Pietersz GA; Loveland BE; Sandrin MS; McKenzie IF;
       Austin Research Institute, Heidelberg, Victoria, Australia.
 SO    Proc Natl Acad Sci U S A. 1995 Oct 24;92(22):10128-32. Unique Identifier
       : AIDSLINE MED/96036037
 AB    The induction of CD8+ cytotoxic T lymphocytes (CTLs) is desirable for
       immunization against many diseases, and recombinant-synthetic peptide
       antigens are now favored agents to use. However, a major problem is how
       to induce CTLs, which requires a T1-type response to such synthetic
       antigens. We report that T1-type (generating high CTL, low antibody) or
       T2-type (the reciprocal) responses can be induced by conjugation of the
       antigen to the carbohydrate polymer mannan: T1 responses are selected by
       using oxidizing conditions; T2 responses are selected by using reducing
       conditions for the conjugation. Using human MUC1 as a model antigen in
       mice, immunization with oxidized mannan-MUC1 fusion protein (ox-M-FP)
       led to complete tumor protection (challenge up to 5 x 10(7) MUC1+ tumor
       cells), CTLs, and a high CTL precursor (CTLp) frequency (1/6900),
       whereas immunization with reduced mannan-MUC1 FP (red-M-FP) led to poor
       protection after challenge with only 10(6) MUC1+ tumor cells, no CTLs,
       and a low CTLp frequency (1/87,800). Ox-M-FP selects for a T1 response
       (mediated here by CD8+ cells) with high interferon gamma (IFN-gamma)
       secretion, no interleukin 4 (IL-4), and a predominant IgG2a antibody
       response; red-M-FP selects for a T2-type response with IL-4 production
       and a high predominant IgG1 antibody response but no IFN-gamma.
 DE    Animal  Antibody Formation  Cells, Cultured  Comparative Study
       Cytokines/BIOSYNTHESIS  Cytotoxicity, Immunologic  CA-15-3
       Antigen/*IMMUNOLOGY  CD8-Positive T-Lymphocytes/IMMUNOLOGY
       Enzyme-Linked Immunosorbent Assay  Female  Human
       IgG/BIOSYNTHESIS/CLASSIFICATION  Interferon Type II/BIOSYNTHESIS
       Interleukin-4/BIOSYNTHESIS  Mannans/*IMMUNOLOGY  Mice  Mice, Inbred BALB
       C  Oxidation-Reduction  Spleen/IMMUNOLOGY  Support, Non-U.S. Gov't
       T-Lymphocyte Subsets/*IMMUNOLOGY  T-Lymphocytes, Cytotoxic/*IMMUNOLOGY
       Tumor Cells, Cultured  3T3 Cells  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

