Download Identification of HLA-A*0201-Restricted CD8+ Cytotoxic T

Identification of HLA-A*0201-Restricted CD8+ Cytotoxic T Lymphocyte Epitopes from Herpes
Simplex Virus Virion Protein 11/12 and 13/14
Christine S. Wang
Mentor: Lbachir BenMohamed
Herpes simplex virus 1 and 2 (HSV-1 and HSV-2), are members of the Herpesviridae family and continue to
be among the most common human pathogens. Despite current drug therapies (Acyclovir and derivatives)
and many other costly prevention measures, the transmission rates and clinical manifestations of HSV-1 and
HSV-2 are increasing. An alternative, cost-effective solution is to develop strong immunotherapeutic and
immunoprophylactic HSV-1 and/or HSV-2 vaccines. However, previous attempts at vaccine development
using live attenuated herpes viruses or entire herpes proteins have been unsuccessful because they produce
pathogenic immune responses and/or fail to induce strong protective CD8+ T cell responses. T cell-mediated
immune responses are believed to play an important role in controlling herpes infection; however, immunedominant responses from HSV envelope glycoproteins have not been enough to be proved as an effective
prophylactic vaccine target. According to recent research, HSV tegument proteins are released into the
cytoplasm during viral entry and hence are among the first viral proteins encountered by an infected cell. To
date, there have been no reports on mapping of MHC Class I-binding CTL epitopes for HSV tegument
protein. The present study focused on identifying candidate epitopes to virion protein 11/12 (VP 11/12), an
abundant HSV tegument protein. We determined ten peptides’ binding affinities to HLA-A*0201 by a MHC
class I stabilization assay previously described by Chentoufi et al. Of the ten proteins, one peptide was
identified as a high affinity HLA-A*0201 binder (VP11/12220-228) and another peptide was identified as a
moderate affinity HLA-A*0201 binder (VP11/12127-135). These peptides are strong candidates for further
investigation in our effort to develop an effective herpes peptide vaccine.