       Document 0523
 DOCN  M9640523
 TI    Generation of diversity in the hierarchy of T-cell epitope responses
       following different routes of immunization with simian immunodeficiency
       virus protein.
 DT    9604
 AU    Brookes R; Bergmeier LA; Mitchell E; Walker J; Tao L; Klavinskis L;
       Meyers NJ; Layton G; Adams SE; Lehner T; Department of Immunology,
       United Medical School, Guy's & St; Thomas' Hospital, London, UK.
 SO    AIDS. 1995 Sep;9(9):1017-24. Unique Identifier : AIDSLINE MED/96085716
 AB    OBJECTIVES: To examine whether the route of immunization determines the
       hierarchy of T-cell epitope proliferative responses in macaques. DESIGN:
       Macaques were immunized with a recombinant simian immunodeficiency virus
       (SIV) p27 core protein by the intramuscular, male and female genital or
       rectal route, each of which was augmented by oral immunization, and by
       the novel targeted lymph-node immunization route. Overlapping peptides
       were used to identify the proliferative T-cell epitopes and to determine
       their hierarchy in the circulation, spleen and lymph nodes. METHODS:
       T-cell epitope mapping of the proliferative responses was studied in
       short-term cell lines. Dendritic cells and macrophages were enriched by
       metrizamide gradient and adherence to plastic, respectively. RESULTS:
       Intramuscular immunization elicited in the circulating T cells a
       hierarchy of T-cell epitopes within four peptides in the following
       descending order of frequency: peptides 121-140 (57.9%), 41-60 (28.9%),
       61-80 (18.9%) and 101-120 (5.4%). The hierarchy of these four T-cell
       epitope responses differed significantly with each of the five routes of
       immunization, when circulating (P < 0.001), splenic (P < 0.02-< 0.001)
       or iliac lymph-node cells (P < 0.001) were analysed. The effect of
       antigen-presenting cells was then investigated and enriched dendritic
       cells were more effective than macrophages in processing and presenting
       the p27 antigen and the immunodominant (121-140) and 61-80 T-cell
       epitopes. CONCLUSIONS: The route of immunization may determine the
       hierarchy of T-cell epitopes in the lymph nodes draining the mucosa in
       the circulating and splenic lymphocytes. The diversity of T-cell
       epitopes may affect the control of HIV at different anatomical sites,
       the administration route of the vaccine, and selection of polypeptides
       or recombinant antigens for immunization.
 DE    Animal  Cell Line  Comparative Study  Drug Administration Routes  Female
       Gene Products, gag/*IMMUNOLOGY  Lymphocyte Transformation/IMMUNOLOGY
       Macaca  Male  Support, Non-U.S. Gov't  SIV/*IMMUNOLOGY  T-Lymphocyte
       Subsets/*IMMUNOLOGY  Vaccines, Synthetic/ADMINISTRATION &
       DOSAGE/*IMMUNOLOGY  Viral Vaccines/ADMINISTRATION & DOSAGE/*IMMUNOLOGY
       JOURNAL ARTICLE

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

