Tat _28-35 SL8-Specific CD8 ⁺ T Lymphocytes Are More Effective than Gag _181-189 CM9-Specific CD8 ⁺ T Lymphocytes at Suppressing Simian Immunodeficiency Virus Replication in a Functional In Vitro Assay

Abstract

Epitope-specific CD8؉ T lymphocytes may play an important role in controlling human immunodeficiency virus (HIV)/simian immunodeficiency virus replication. Unfortunately, standard cellular assays do not measure the antiviral efficacy (the ability to suppress virus replication) of CD8 ؉ T lymphocytes. Certain epitopespecific CD8؉ T lymphocytes may be better than others at suppressing viral replication. We compared the antiviral efficacy of two immunodominant CD8 ؉ T lymphocyte responses-Tat 28-35 SL8 and Gag 181-189CM9-by using a functional in vitro assay. Viral suppression by Tat-specific CD8 ؉ T lymphocytes was consistently greater than that of Gag-specific CD8 ؉ T lymphocytes. Such differences in antigen-specific CD8 ؉ -T-lymphocyte efficacy may be important for selecting CD8 ؉ T lymphocyte epitopes for inclusion in future HIV vaccines.

Killing Kinetics of Simian Immunodeficiency Virus-Specific CD8+ T Cells: Implications for HIV Vaccine Strategies

“…The KP9/Gag-specific CD8 ϩ T cells induced by prime-boost vaccination are poorly loaded with preformed intracellular granzyme B and perforin and therefore cannot rapidly release large amounts of these effector molecules. We confirmed these findings of poor loading of granzyme B and slow killing capacity of CTLs in stored PBMC samples from the VV/FPV-vaccinated animals at earlier time points (weeks [12][13][14] postvaccination (data not shown). Although it was not always possible to acquire a large number of KP9-specific cells at multiple time points from the small quantities of frozen PBMC available, we did detect slow cytolysis phenotypes from animals receiving DNA and FPV prime-boost vaccinations as well as other animals receiving VV/FPV vaccinations (data not shown), confirming our data using fresh samples.…”

Simian Immunodeficiency Virus SIVmac239 Infection of Major Histocompatibility Complex-Identical Cynomolgus Macaques from Mauritius

“…These studies could directly test the hypothesis that the failure of cellular immunity to control SIV infection results from an inability of CTL to mobilize to sites of viral replication early during infection (33). Additionally, in vitro data suggest that certain CTL specificities suppress SIV and HIV replication far more effectively than others (24,43). The use of MCM for adoptive transfers of individual CTL specificities could provide a useful method for both identifying and characterizing the shared biological attributes of effective CTL response.…”

Portable flanking sequences modulate CTL epitope processing

“…In the chronic phase of HIV infection, an average of 5 to 27 different epitopes are targeted in a given individual (9,14,(16)(17)(18)20). Multiple reports have shown that there is no consistent relationship between magnitude or breadth of these IFN-γ responses and viral load (9,14,15,(21)(22)(23), suggesting that they my differ in their antiviral potential (16,(24)(25)(26)(27). Immunodominant responses are not necessarily protective (28) whereas some subdominant responses have been associated with lower viral loads (22,23).…”