Projects per year
Antigen immunodominance is an unexplained feature of CD8+ T cell responses to herpesviruses, which are agents whose lytic replication involves the sequential expression of immediate early (IE), early (E), and late (L) proteins. Here, we analyze the primary CD8 response to Epstein-Barr virus (EBV) infection for reactivity to 2 IE proteins, 11 representative E proteins, and 10 representative L proteins, across a range of HLA backgrounds. Responses were consistently skewed toward epitopes in IE and a subset of E proteins, with only occasional responses to novel epitopes in L proteins. CD8+ T cell clones to representative IE, E, and L epitopes were assayed against EBV-transformed lymphoblastoid cell lines (LCLs) containing lytically infected cells. This showed direct recognition of lytically infected cells by all three sets of effectors but at markedly different levels, in the order IE > E > L, indicating that the efficiency of epitope presentation falls dramatically with progress of the lytic cycle. Thus, EBV lytic cycle antigens display a hierarchy of immunodominance that directly reflects the efficiency of their presentation in lytically infected cells; the CD8+ T cell response thereby focuses on targets whose recognition leads to maximal biologic effect.
- Antibody Affinity
- Antigen Presentation
- CD8-Positive T-Lymphocytes
- Epstein-Barr Virus Infections
- Epstein-Barr Virus Nuclear Antigens
- HLA Antigens
- Immunodominant Epitopes
- Virus Replication
FingerprintDive into the research topics of 'CD8+ immunodominance among Epstein-Barr virus lytic cycle antigens directly reflects the efficiency of antigen presentation in lytically infected cells'. Together they form a unique fingerprint.
- 1 Finished
Cellular Immunity to Herpesvirus Infection: Studies with Epstein-Barr Virus and Human Cytomegalovirus
1/09/05 → 31/08/10
Project: Research Councils