Limiting dilution analysis of cytotoxic T lymphocytes to human immunodeficiency virus gag antigens in infected persons: in vitro quantitation of effector cell populations with p17 and p24 specificities.

Koup, Richard A.; Pikora, Cheryl; Luzuriaga, Katherine; Brettler, Doreen B.; Day, Eric S.; Mazzara, Gail P.; Sullivan, John L.

doi:10.1084/jem.174.6.1593

Cited by 103 publications

(51 citation statements)

References 30 publications

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“…Specific sequences in Gag and Nef serve as MHC-I-restricted epitopes for CTL recognition (20,31,34). Sequence variations in these proteins can result in escape from CTL recognition.…”

Section: Analysis Of Hiv-1 Second-receptor Genotypesmentioning

confidence: 99%

Unusual Polymorphisms in Human Immunodeficiency Virus Type 1 Associated with Nonprogressive Infection

Alexander

Weiskopf

Greenough

et al. 2000

J Virol

147

111

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Factors accounting for long-term nonprogression may include infection with an attenuated strain of human immunodeficiency virus type 1 (HIV-1), genetic polymorphisms in the host, and virus-specific immune responses. In this study, we examined eight individuals with nonprogressing or slowly progressing HIV-1 infection, none of whom were homozygous for host-specific polymorphisms (CCR5-⌬32, CCR2-64I, and SDF-1-3A) which have been associated with slower disease progression. HIV-1 was recovered from seven of the eight, and recovered virus was used for sequencing the full-length HIV-1 genome; full-length HIV-1 genome sequences from the eighth were determined following amplification of viral sequences directly from peripheral blood mononuclear cells (PBMC). Longitudinal studies of one individual with HIV-1 that consistently exhibited a slow/low growth phenotype revealed a single amino acid deletion in a conserved region of the gp41 transmembrane protein that was not seen in any of 131 envelope sequences in the Los Alamos HIV-1 sequence database. Genetic analysis also revealed that five of the eight individuals harbored HIV-1 with unusual 1-or 2-amino-acid deletions in the Gag sequence compared to subgroup B Gag consensus sequences. These deletions in Gag have either never been observed previously or are extremely rare in the database. Three individuals had deletions in Nef, and one had a 4-amino-acid insertion in Vpu. The unusual polymorphisms in Gag, Env, and Nef described here were also found in stored PBMC samples taken 3 to 11 years prior to, or in one case 4 years subsequent to, the time of sampling for the original sequencing. In all, seven of the eight individuals exhibited one or more unusual polymorphisms; a total of 13 unusual polymorphisms were documented in these seven individuals. These polymorphisms may have been present from the time of initial infection or may have appeared in response to immune surveillance or other selective pressures. Our results indicate that unusual, difficult-to-revert polymorphisms in HIV-1 can be found associated with slow progression or nonprogression in a majority of such cases.

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“…Specific sequences in Gag and Nef serve as MHC-I-restricted epitopes for CTL recognition (20,31,34). Sequence variations in these proteins can result in escape from CTL recognition.…”

Section: Analysis Of Hiv-1 Second-receptor Genotypesmentioning

confidence: 99%

Unusual Polymorphisms in Human Immunodeficiency Virus Type 1 Associated with Nonprogressive Infection

Alexander

Weiskopf

Greenough

et al. 2000

J Virol

147

111

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“…The potential role of CD8+, cytolytic T lymphocytes' (CTLs) in resistance to infectious and malignant diseases has been reem- 1. Abbreviations used in this paper: APC, antigen presenting cells; CTL, cytolytic T lymphocytes; ER+, T cell enriched; ER-, T cell depleted; HA, hemagglutinin; HRP, horseradish peroxidase; LCMV, lymphocytic choriomeningitis virus; MLR, mixed leukocyte reaction; NK, natural killer cells; NP, nucleoprotein; PE, phycoerythrin.…”

Section: Introductionmentioning

confidence: 99%

“…Antigen-specific CTLs are recognized as a possible defense mechanism in infection with HIV-1 (1)(2)(3), cytomegalovirus (4), and in malaria (5). Antigens that are recognized by melanoma-specific CTLs have also been identified by Van der Bruggen et al (6) and Brichard et al (7).…”

Section: Introductionmentioning

confidence: 99%

Influenza virus-infected dendritic cells stimulate strong proliferative and cytolytic responses from human CD8+ T cells.

Bhardwaj¹,

Bender²,

González³

et al. 1994

J. Clin. Invest.

254

170

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Antigen-specific, CD8+, cytolytic T lymphocytes (CTLs) could potentially provide resistance to several infectious and malignant diseases. However, the cellular requirements for the generation of specific CTLs in human lymphocyte cultures are not well defined, and repetitive stimulation with antigen is often required. We find that strong CD8+ CTL responses to influenza virus can be generated from freshly isolated blood T cells, as long as dendritic cells are used as antigen presenting cells (APCs). Small numbers of dendritic cells (APC:T cell ratio of 1:50-1:100) induce these CTL responses from most donors in 7 d of culture, but monocytes are weak or inactive. Whereas both dendritic cells and monocytes are infected with influenza virus, the former serve as effective APCs for the induction of CD8+ T cells while the latter act as targets for the CTLs that are induced. The strong CD8+ response to influenza virus-infected dendritic cells is accompanied by extensive proliferation of the CD8+ T cells, but the response can develop in the apparent absence of CD4+ helpers or exogenous lymphokines. CD4+ influenza virus-specific CTLs can also be induced by dendritic cells, but the cultures initially must be depleted of CD8+ cells. These findings should make it possible to use dendritic cells to generate human, antigen-specific, CD8+ CTLs to other targets. The results illustrate the principle that efficient T cell-mediated responses develop in two stages: an afferent limb in which dendritic cells are specialized APCs and an efferent limb in which the primed T cells carry out an immune response to many types of presenting cells. (J. Clin. Invest. 1994. 94:797-807.)

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“…As in the case of pl8gag, plI 5gag was recognized by approximately half of p55Saa-specific cell lines, whereas p245ag was recognized by almost all of them [19,40].…”

Section: Discussionmentioning

confidence: 99%

Multispecific and heterogeneous recognition of the gag protein by cytotoxic T lymphocytes (CTL) from HIV-infected patients: factors other than the MHC control the epitopic specificities

Buseyne

Janvier

Fleury

et al. 1994

Clinical and Experimental Immunology

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SUMMARYThe HIV gag polyprotein is a major target for recognition by CTL in infected humans. Using recombinant vaccinia viruses (rW) expressing truncations of the p24gag, and the p18gag, pl5gag and HIV-2 p565ag proteins, the characterization of epitope regions recognized by in vitrostimulated peripheral blood mononuclear cells (PBMC) from 18 infected patients has been studied. The gag-specific response of most individuals is polyclonal and multispecific, and interindividual variations between target epitope regions were frequently observed, despite shared MHC alleles. As CTL may play an important role in the control of HIV replication in infected hosts, these results have important implications for designing vaccine strategies.

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Limiting dilution analysis of cytotoxic T lymphocytes to human immunodeficiency virus gag antigens in infected persons: in vitro quantitation of effector cell populations with p17 and p24 specificities.

Cited by 103 publications

References 30 publications

Unusual Polymorphisms in Human Immunodeficiency Virus Type 1 Associated with Nonprogressive Infection

Unusual Polymorphisms in Human Immunodeficiency Virus Type 1 Associated with Nonprogressive Infection

Influenza virus-infected dendritic cells stimulate strong proliferative and cytolytic responses from human CD8+ T cells.

Multispecific and heterogeneous recognition of the gag protein by cytotoxic T lymphocytes (CTL) from HIV-infected patients: factors other than the MHC control the epitopic specificities

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