Abstract
BackgroundVery little is known about the immunodominance patterns of HIV-1-specific T cell responses during primary HIV-1 infection and the reasons for human lymphocyte antigen (HLA) modulation of disease progression.Methods and FindingsIn a cohort of 104 individuals with primary HIV-1 infection, we demonstrate that a subset of CD8+ T cell epitopes within HIV-1 are consistently targeted early after infection, while other epitopes subsequently targeted through the same HLA class I alleles are rarely recognized. Certain HLA alleles consistently contributed more than others to the total virus-specific CD8+ T cell response during primary infection, and also reduced the absolute magnitude of responses restricted by other alleles if coexpressed in the same individual, consistent with immunodomination. Furthermore, individual HLA class I alleles that have been associated with slower HIV-1 disease progression contributed strongly to the total HIV-1-specific CD8+ T cell response during primary infection.ConclusionsThese data demonstrate consistent immunodominance patterns of HIV-1-specific CD8+ T cell responses during primary infection and provide a mechanistic explanation for the protective effect of specific HLA class I alleles on HIV-1 disease progression.
Highlights
The majority of individuals infected with HIV-1 develop an acute viral syndrome within 7–21 days of infection, characterized primarily by fever, lymphadenopathy, and cutaneous rash in the presence of very high levels of HIV-1 replication [1,2]
In a cohort of 104 individuals with primary HIV-1 infection, we demonstrate that a subset of CD8þ T cell epitopes within HIV-1 are consistently targeted early after infection, while other epitopes subsequently targeted through the same human lymphocyte antigen (HLA) class I alleles are rarely recognized
Despite this presumed immune-mediated decline in acute viremia, HIV-1-specific CD8þ T cell responses in primary infection are of lower magnitude and more narrowly directed against a limited number of epitopes than are HIV-1-specific CD8þ T cell responses detected in chronic infection [12,13,14,15], indicating that the quality and specificity, rather than the quantity, of virus-specific CD8þ T cell responses may be associated with the initial control of viral replication [16,17,18,19,20]
Summary
The majority of individuals infected with HIV-1 develop an acute viral syndrome within 7–21 days of infection, characterized primarily by fever, lymphadenopathy, and cutaneous rash in the presence of very high levels of HIV-1 replication [1,2]. The first appearance of HIV-1-specific CD8þ T cells in the peripheral blood has been shown to be temporally associated with the initial decline of HIV-1 viremia during primary infection [3,4], suggesting a crucial role of these early virus-specific T cells in the control of viral replication This is further supported by the lack of decline in viral replication in simian immunodeficiency virusinfected macaques depleted of CD8þ lymphocytes [5,6,7] and the selection of viral strains containing sequence variations within targeted CD8þ T cell epitopes during this early phase of infection [8,9,10,11], indicative of HLA class I-restricted immune selection pressure on the virus. Why the amount of virus drops after initial infection is not fully understood, but there is good evidence that the white blood cells called CD8 T lymphocytes, which can kill other cells infected with viruses, are at least partially responsible for initially bringing HIV infection under control
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
