Characterization of human immunodeficiency virus type 1-specific cytotoxic T lymphocyte clones isolated during acute seroconversion: recognition of autologous virus sequences within a conserved immunodominant epitope.

Abstract

SummaryVirus-specific cytotoxic T lymphocytes (CTL) are involved in protective immunity to many virus infections. It has recently been shown that CTL are detectable early during primary infection with the primate lentiviruses, human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus. To better characterize the CTL response during acute HIV-1 infection, HIV-l-specific CTL clones were generated from two patients during symptomatic HIV-1 seroconversion. These CTL clones demonstrated specificity for env of HIV-1 and recognized sequences within gp41. Two human histocompatibility leukocyte antigen (HLA) A31-restricted clones from the same individual were found to have differing virus strain specificities. Both dones recognized the 11-amino acid peptide RLRDLLLIVTR from position 770-780 of glYll. A change from T to V at position 779 in this epitope abrogated lysis by one done but not the other. A CTL clone from the other patient, restricted by a different class I HLA allele, recognized the nine-amino acid peptide HRLRDLLLI from position 769-777 of gp41. Of note, the peptide RLRDLLLIVTR has been shown by others to be presented to CTL by HLA-A3.1. Autologous virus sequences from seroconversion and up to 15 wk after presentation in these two patients were recognized by the CTL clones isolated during acute infection. None of the CTL clones recognized the MN strain of HIV-1, indicating the problems inherent in relying on a single virus strain in the development of a vaccine. These studies have identified an immunodominant and promiscuous area for the generation of CTL responses within gp41. This recognit/on of autologous virus sequences by the initial CTL response is consistent with the hypothesis that a single virus strain is transmitted to the seroconverter and that the CTL response is involved in the initial control of that virus. These studies indicate the importance of the CTL response to HIV-1 infection and have implications in the design of vaccines.cute infection with HIV-1 is characterized by fever, rash, and lymphadenopathy (1) in association with high levels of virus replication (2-4). These high virus titers dramatically decline over the ensuing weeks, coinciding with the

Dynamics of viral replication in infants with vertically acquired human immunodeficiency virus type 1 infection.

“…The presence of autochthonous antibodies binding to several HIV-1 gag and envelope epitopes, could be documented in 3 out of 4 rapid progressors, and 4 out of 5 slow progressors early in life (8; and unpublished results); therefore, in agreement with other studies (32,33), such antibodies did not appear to play a critical role in determining the pattern of infection. As viral decline after primary infection in adults has mainly been associated with the emergence of HIV-1 specific cytotoxic T lymphocytes (CTL) (34)(35)(36), the viral decline observed in slow progressors might indicate that these infants were able to mount a cellular immune response, and partially control HIV-1 replication. Nonetheless, in agreement with a recent observation (37), it is noteworthy that the viral clearance in these infants was consistently lower than that observed in adults after primary infection, in whom a viral decline by a factor of 100 to 1000 was described (15,16).…”

Absence of Immunodominant Anti-Gag p17 (SL9) Responses among Gag CTL-Positive, HIV-Uninfected Vaccine Recipients Expressing the HLA-A*0201 Allele

“…First, CTL activity has been correlated with the initial decrease in viremia during the acute phase of infection in human HIV infection as well in SIV-infected macaques (5)(6)(7)(8)(9)(10)(11)(12). In both HIV-infected patients as well as SIV models, the occurrence of escape mutants is detectable within the first few months of infection, suggesting that CTLs exert considerable selective pressure on the replicating virus population (13,14).…”

SIV infection of macaques - modeling the progression to AIDS dementia

“…HIV-and SIV-speci®c CTL have been isolated from peripheral blood and from lymphoid tissues early after infection and are associated with the control of primary viremia Hadida et al, 1992;Koup et al, 1994;Pantaleo et al, 1994;Reimann et al, 1994;Safrit et al, 1994;Yasutomi et al, 1993). CTL have also been identi®ed in the CSF of HIV-infected individuals, but it is not known whether these cells actually traverse the brain parenchyma and drain to the CSF or are made in the meninges.…”