Biology Reference
In-Depth Information
T A B L E
6.1. (Continued)
Integrase
FLDGIDKAQDEHEKYHSNWRAMASDFNLPPVVAKEIVASCDKCQLKGEAMHGQVDCSPGIW
QLDCTHLEGKVILVAVHVASGYIEAEVIPAETGQETAYFLLKLAGRWPVKTIHTDNGSNFT
GATVRAACWWAGIKQEFGIPYNPQSQGVVESMNKELKKIIGQVRDQAEHLKTAVQMAVFIH
NFKRKGGIGGYSAGERIVDIIATDIQTKELQKQITKIQNFRVYYRDSRNPLWKGPAKLLWK
GEGAVVIQDNSDIKVVPRRKAKIIRDYGKQMAGDDCVASRQDED
280
Nef
MGGKWSKSSVIGWPTVRERMRRAEPAADRVGAASRDLEKHGAITSSNTAATNAACAWLEAQ
EEEEVGFPVTPQVPLRPMTYKAAVDLSHFLKEKGGLEGLIHSQRRQDILDLWIYHTQGYFP
DXQNYTPGPGVRYPLTFGWCYKLVPVEPDKIEEANKGENTSLLHPVSLHGMDDPEREVLEW
RFDSRLAFHHVARELHPEYFKNC
200
Our current knowledge of HIV-speci®c CTL generation in vivo indicates
that APCs play a crucial role (Knight et al., 1997; Plata et al., 1990). In het-
erosexual transmission, for example, it is believed that subepithelial dendritic
cells play a role by picking, processing, and transporting macrophage-trophic
virus across the genital epithelium and transferring the virus to activated
CD4
T cells expressing the CCR5 coreceptor. Some immature dendritic cells
are believed to carry the virus along the lymphatic routes (where they mature
along the way) to the lymph nodes, where the virus is transferred to T cells
(Cameron et al., 1996). Dendritic cells have the ability to activate some resting
T cells, making them susceptible to HIV (Cameron et al., 1994; Zarling et al.,
1999). Following this initial infection, the virus replicates in CD4
cells, caus-
ing infected-cell death and at the same time inducing both cellular and humoral
immunity, which is usually evident by 3±6 months after infection. Macrophages
also play a signi®cant but less potent role in transferring HIV to T cells. Mac-
rophages have an additional role of supporting HIV replication, mainly of the
macrophage-trophic, nonsyncytium-inducing ( NSI ) viral subtype usually in-
volved in initial infection. Although HIV-speci®c antibodies usually persist for
life, CTL responses are variable over time, even within the same individual. We
will discuss these changes and trends in the relevant sections below.
GENERATION OF CTL IN VITRO
Most of our understanding of CTL functions arose from in vitro studies, which
are aimed at amplifying memory T cells by secondary stimulation using rele-
vant antigens and autologous APCs (Zarling et al., 1999). Table 6.2 lists the
most commonly used in vitro assays for CD8
cell function. These tests can
be conveniently divided into measurements for constitutively secreted lympho-
kines, extent of fragmentation of target cell DNA, and studies of membrane
integrity of target cells.
