Toggle Main Menu Toggle Search

Open Access padlockePrints

Repertoire of HLA-DR1-Restricted CD4 T-Cell Responses to Capsular Caf1 Antigen of Yersinia pestis in Human Leukocyte Antigen Transgenic Mice

Lookup NU author(s): Professor John Robinson

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


Abstract

Yersinia pestis is the causative agent of plague, a rapidly fatal infectious disease that has not been eradicated worldwide. The capsular Caf1 protein of Y. pestis is a protective antigen under development as a recombinant vaccine. However, little is known about the specificity of human T-cell responses for Caf1. We characterized CD4 T-cell epitopes of Caf1 in "humanized" HLA-DR1 transgenic mice lacking endogenous major histocompatibility complex class II molecules. Mice were immunized with Caf1 or each of a complete set of overlapping synthetic peptides, and CD4 T-cell immunity was measured with respect to proliferative and gamma interferon T-cell responses and recognition by a panel of T-cell hybridomas, as well as direct determination of binding affinities of Caf1 peptides to purified HLA-DR molecules. Although a number of DR1-restricted epitopes were identified following Caf1 immunization, the response was biased toward a single immunodominant epitope near the C terminus of Caf1. In addition, potential promiscuous epitopes, including the immunodominant epitope, were identified by their ability to bind multiple common HLA alleles, with implications for the generation of multivalent vaccines against plague for use in humans.


Publication metadata

Author(s): Musson JA, Ingram R, Durand G, Ascough S, Waters EL, Hartley MG, Robson T, Maillere B, Williamson ED, Sriskandan S, Altmann D, Robinson JH

Publication type: Article

Publication status: Published

Journal: Infection and Immunity

Year: 2010

Volume: 78

Issue: 10

Pages: 4356-4362

Print publication date: 26/07/2010

ISSN (print): 0019-9567

ISSN (electronic): 1098-5522

Publisher: American Society for Microbiology

URL: http://dx.doi.org/10.1128/IAI.00195-10

DOI: 10.1128/IAI.00195-10


Altmetrics

Altmetrics provided by Altmetric


Funding

Funder referenceFunder name
HHSN266200400084CNIH-NIAID

Share