Vaccine 24 (2006) 597–606 The MHC-haplotype influences primary, but not memory, immune responses to an immunodominant peptide containing T- and B-cell epitopes of the caprine arthritis encephalitis virus Gag protein Alexandra Fluri a,b,1 , Chiara Nenci a,1 , Marie-Luise Zahno a , Hans-Rudolf Vogt a , Shiv Charan a , Andr´ e Busato b , Gianfranco Pancino c , Ernst Peterhans a , Gabriela Obexer-Ruff b , Giuseppe Bertoni a,∗ a Institute of Veterinary Virology, University of Berne, Laenggass-Strasse 122, CH-3012 Berne, Switzerland b Institute for Animal Breeding, University of Berne, Berne, Switzerland c Unit´ e de Biologie des R´ etrovirus, D´ epartement de Virologie Institut Pasteur, 75724 Paris, France Received 31 May 2005; received in revised form 25 July 2005; accepted 9 August 2005 Available online 19 August 2005 Abstract In this report, we describe a short peptide, containing a T helper- and a B-cell epitope, located in the Gag protein of the caprine arthritis encephalitis virus (CAEV). This T-cell epitope is capable of inducing a robust T-cell proliferative response in vaccinated goats with different genetic backgrounds and to provide help for a strong antibody response to the B-cell epitope, indicating that it may function as a universal antigen-carrier for goat vaccines. The primary immune response of goats homozygous for MHC class I and II genes showed an MHC-dependent partitioning in rapid-high and slow-low responses, whereas the memory immune response was strong in both groups, demonstrating that a vaccine based on this immunodominant T helper epitope is capable to overcome genetic differences. © 2005 Elsevier Ltd. All rights reserved. Keywords: T-cell epitope; MHC; Immunological memory; B-cell epitope; Carrier protein; Goat; Ruminant; Caprine arthritis encephalitis virus, CAEV 1. Introduction The natural immune response to lentiviruses, such as the human immunodeficiency virus (HIV) or caprine arthri- tis encephalitis virus (CAEV) is inadequate to clear the virus, thus, permitting these viruses to establish lifelong per- sistence in the infected host [1–3]. However, the immune response is sufficient to keep virus replication at a low level, thus, slowing down the progress to disease. CAEV and HIV share their tropism for monocytes/macrophages and dendritic cells but differ in their ability to infect T-cells, which are the main target of HIV but cannot be infected by CAEV. For both CAEV and HIV a high viral load corre- ∗ Corresponding author. Tel.: +41 31 631 24 83; fax: +41 31 631 25 34. E-mail address: bertoni@ivv.unibe.ch (G. Bertoni). 1 These two authors equally contributed to this project. lates with the development of pathological sequela, such as arthritis or acquired immunodeficiency syndrome (AIDS), respectively. T helper cells play a pivotal role in the immune defense against lentiviral infections, both directly as effector cells and by providing help to B and cytotoxic T-cells. In HIV infected patients the proliferative response of CD4 positive helper T-cells to HIV antigens and especially to the Gag pro- tein is a major correlate of protection in persistently infected, long-term non-progressors [4,5]. In CAEV infected goats, an impaired T-cell proliferative activity has been shown to correlate with the subsequent development of arthritis and a higher viral load [6]. For both lentiviral infections it has been hypothesized that not only the strength but also the quality of the T helper cell immune response, for instance the spectrum of cytokines produced, may influence the efficiency of the immune response [7,8]. 0264-410X/$ – see front matter © 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.vaccine.2005.08.043