Immune Responses Against Conserved and Variable Viral Epitopes
نویسندگان
چکیده
We extend well-known mathematical models of viral infection to examine the response of cytotoxic T lymphocytes (CTL) to both conserved and variable viral epitopes. Because most viruses are subject to error-prone reproduction, CTL recognition may be faced with highly variable epitopes, while other CTL epitopes may remain conserved across viral strains. In this paper we examine the steady state conditions for a simple model of viral-immune system dynamics in which the viral strain can be limited by either a specific immune response, a cross-reactive immune response, or host cell availability. We find that the most important factors determining the type of immune response elicited and viral diversity are the relative proliferation rates of the two types of immune response. If the immune response to variable epitopes is strong compared with the response to conserved epitopes, diversity will be negatively correlated with the total burden of infected cells. In this situation high diversity may be indicative of a strong immune response and slower disease progression. In contrast, for patients whose immune response is directed predominantly towards conserved viral epitopes, our model predicts that diversity and viral load will be posirively correlated.
منابع مشابه
Superior Control of HIV-1 Replication by CD8+ T Cells Targeting Conserved Epitopes: Implications for HIV Vaccine Design
A successful HIV vaccine will likely induce both humoral and cell-mediated immunity, however, the enormous diversity of HIV has hampered the development of a vaccine that effectively elicits both arms of the adaptive immune response. To tackle the problem of viral diversity, T cell-based vaccine approaches have focused on two main strategies (i) increasing the breadth of vaccine-induced respons...
متن کاملTargeting of conserved gag-epitopes in early HIV infection is associated with lower plasma viral load and slower CD4(+) T cell depletion.
We aimed to investigate whether the character of the immunodominant HIV-Gag peptide (variable or conserved) targeted by CD8(+) T cells in early HIV infection would influence the quality and quantity of T cell responses, and whether this would affect the rate of disease progression. Treatment-naive HIV-infected study subjects within the OPTIONS cohort at the University of California, San Francis...
متن کاملImmunogenicity of a New HIV-1 DNA Construct in a BALB/c Mouse Model
Background: Cell mediated immunity, especially cytotoxic T cell responses against HIV-1 infection, plays a critical role in controlling viral replication and disease progres-sion. DNA vaccine is a novel technology which is known to stimulate strong cellular immune responses. Many DNA vaccines have been tested for HIV infection but there is still no effective vaccine against this infection. Cons...
متن کاملHIV-1 Group M Conserved Elements Vaccine
Recent HIV vaccine designs have sought to block viral escape pathways by compressing antigenic diversity. In light of HIV’s propensity to mutate and thereby to ever ramify viral populations, could it be that providing sufficient protection against global diversity is an insurmountable problem? We propose an alternative HIV-1 vaccine design that deliberately includes viral segments conserved acr...
متن کاملConserved HIV-1 epitopes continuously elicit subdominant cytotoxic T-lymphocyte responses.
BACKGROUND The epitope specificities and antiviral activities of class I HLA-restricted CD8(+) T cells, especially those induced during human immunodeficiency virus type 1 (HIV-1) primary infection, are important considerations in designing HIV-1 vaccines. Conserved epitopes may be more commonly and persistently recognized than variable epitopes, as they may be more likely to be present in infe...
متن کامل