4.2 Background and Purpose 
4.2.1 HIV-1 and the Immune System 
4.2. 1 . 1 Although nearly all HIV-1 infected persons develop antibodies, such 
antibodies appear to be unable to clear the HTV-1 infection 1. Most HTV- 
1 vaccines and immunotherapeutics studied to date have generated HTV- 
1 reactive antibodies, sometimes at high titers, but there is no published 
evidence that these antibody responses prevent disease progression. 
4. 2. 1 . 2 There is strong evidence that the HIV- 1 virus may be directly 
transmitted from infected to non-infected cells through several 
mechanisms, including syncytia formation, without entering the 
extracellular spaced In this circumstance, HIV-1 reactive antibodies 
have no opportunity to intercept the HIV-1 virus. For this reason, there 
is a broad consensus among HIV-1 researchers and clinicians that a 
serious effort to develop HTV-1 reactive cytotoxic T lymphocytes (CTL) 
represents a largely unexplored and potentially crucial frontier in 
controlling the progression to AIDS^. 
4. 2. 1 . 3 HTV-1 is a virus which has evolved the ability to evade and confound 
the immune system as follows: (1) Gene segments coding for its 
envelope protein mutate frequently, including those portions of the 
envelope which are immunodominant with respect to antibody 
production^ and, (2) HIV-1 may down-regulate the concentration of 
major histocompatibility complex (MHC) molecules on the surface of 
cells in which HIV-1 virions are replicating in vitro 5. If MHC down 
regulation is also present in vivo, this may be responsible for lower 
levels of CTL induction, since MHC molecules present foreign antigens 
to the immune system, (3) HTV-1 infects and disables CD4 T-cells, 
which results in the progressive functional loss of this immune cell 
population as the infection spreads^. The consequence of this loss of 
1 Weiss, et al, Nature, 316:69-72 (1989) 
^Popovic, M., et al, Science, 224:497-500 (1984). 
3 Walker, B.D., et al, AIDS, 4: 177-184 (1990). 
4 La Rosa, G. J„ et al. Science, 249:932-935 (1990). 
5 Scheppler, J.A., et al. J. Clin. Invest.. 72:398 (1983). 
^Rosenberg, Z.F., et al, AIDS Res. and Human Retroviruses, 5:104 (1989). 
Recombinant DNA Research, Volume 17 
