Pimelautide or Trimexautide as Built-in Adjuvants Associated with an HIV-1-Derived Peptide: Synthesis and in Vivo Induction of Antibody and Virus-Specific Cytotoxic T-Lymphocyte-Mediated Response

1995 ◽  
Vol 38 (3) ◽  
pp. 459-465 ◽  
Author(s):  
Benoit Deprez ◽  
Helene Gras-Masse ◽  
Frederic Martinon ◽  
Elisabeth Gomard ◽  
Jean-Paul Levy ◽  
...  
Keyword(s):  
Peptide Synthesis ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Hiv 1 ◽  
In Vivo Induction

scholarly journals Inefficient Cytotoxic T Lymphocyte–Mediated Killing of HIV-1–Infected Cells In Vivo

PLoS Biology ◽  
2006 ◽  
Vol 4 (4) ◽  
pp. e90 ◽  
Author(s):  
Becca Asquith ◽  
Charles T. T Edwards ◽  
Marc Lipsitch ◽  
Angela R McLean
Keyword(s):  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Infected Cells ◽  
Hiv 1

Studies on in Vivo Induction of Cytotoxic T Lymphocyte Responses by Synthetic Peptides from E6 and E7 Oncoproteins of Human Papillomavirus Type 16

1995 ◽  
Vol 8 (3) ◽  
pp. 165-174 ◽  
Author(s):  
ASIS K. SARKAR ◽  
GUILLERMO TORTOLERO-LUNA ◽  
PRAMOD N. NEHETE ◽  
RALPH B. ARLINGHAUS ◽  
MICHELE FOLLEN MITCHELL ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
T Lymphocyte ◽  
Synthetic Peptides ◽  
Cytotoxic T Lymphocyte ◽  
Human Papillomavirus Type 16 ◽  
E6 And E7 Oncoproteins ◽  
E6 And E7 ◽  
Lymphocyte Responses ◽  
In Vivo Induction

scholarly journals T cell receptor usage and fine specificity of human immunodeficiency virus 1-specific cytotoxic T lymphocyte clones: analysis of quasispecies recognition reveals a dominant response directed against a minor in vivo variant.

1996 ◽  
Vol 183 (4) ◽  
pp. 1669-1679 ◽  
Author(s):  
S A Kalams ◽  
R P Johnson ◽  
M J Dynan ◽  
K E Hartman ◽  
T Harrer ◽  
...  
Keyword(s):  
T Cell Receptor ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Cell Receptor ◽  
Ctl Response ◽  
Immunodeficiency Virus ◽  
Hla Type ◽  
A Minor ◽  
Hiv 1

Numerous virus-specific, class I-restricted cytotoxic T lymphocyte (CTL) epitopes have been identified, yet little information is available regarding the specificity of the CTL response in persons of the same human histocompatibility leukocyte antigen (HLA) type. In this study, the human immunodeficiency virus (HIV) 1 envelope-specific CTL response was evaluated in five HLA-B14-positive persons. CTL responses specific for a previously described nine-amino acid epitope in gp41 (aa 584-592, ERYLKDQQL) could be identified in all subjects, and CTL clones specific for this epitope could be isolated from four persons. Despite heterogeneous T cell receptor usage, the fine specificity of the clones was similar, as defined by recognition of alanine-substituted peptides as well as peptides representing natural HIV-1 sequence variants. Correlation with in vivo virus sequences revealed that the dominant species in two of the subjects represented poorly recognized variants, with a K-->Q substitution at amino acid 588, whereas no variants were observed in the other two subjects. Although clonal type-specific responses to these dominant variants could be identified, the magnitude of these responses remained small, and the dominant CTL response was directed at the minor in vivo variant. These studies indicate that despite similar epitope-specific immunologic pressure in persons of the same HLA type, the in vivo quasispecies may differ, and that the major in vivo immune response to a given CTL epitope can be directed at a minor variant.

Cytotoxic T lymphocytes and viral evolution in primary HIV-1 infection*

1999 ◽  
Vol 97 (6) ◽  
pp. 707-718 ◽  
Author(s):  
David A. PRICE ◽  
Chris A. O'CALLAGHAN ◽  
Joseph A. WHELAN ◽  
Philippa J. EASTERBROOK ◽  
Rodney E. PHILLIPS
Keyword(s):  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Viral Evolution ◽  
Case Series ◽  
Effector Cells ◽  
Lymphocyte Responses ◽  
Hiv 1

Efforts to develop immune-based therapies for HIV infection have been impeded by incomplete definition of the immunological correlates of protection. Despite many precedents demonstrating that CD8+ cytotoxic T lymphocytes are key mediators of protective anti-viral immunity in non-human animal models, direct evidence that these effector cells control viral replication in HIV-1 infection has remained elusive. The first part of this paper describes a detailed immunological and genetic study founded on evolutionary considerations. Following infection with HIV-1, virus variants which escaped recognition by autologous cytotoxic T lymphocytes were shown to possess a selection advantage within the host environment. Cytotoxic T lymphocytes therefore exert anti-viral pressure in vivo. This observation provides compelling evidence that cytotoxic T lymphocytes comprise a significant element of anti-retroviral immunity. Subsequently, the quantification of peripheral cytotoxic T lymphocyte frequencies utilizing peptide–(human leucocyte antigen class I) tetrameric complexes is described. Five patients with qualitatively similar immunodominant cytotoxic T lymphocyte responses during symptomatic primary HIV-1 infection were studied longitudinally. Expansions of virus-specific CD8+ lymphocytes comprising up to 2% of the total CD8+ T cell population were observed in the acute phase of infection. Antigenic load was identified as an important determinant of circulating HIV-1-specific CD8+ lymphocyte levels; however, significant numbers of such cells were also found to persist following prolonged therapeutic suppression of plasma viraemia. In addition, an analysis of antigenic sequence variation with time in this case series suggests that the early administration of combination anti-retroviral therapy may limit HIV-1 mutational escape from host cytolytic specificities. The implications of these preliminary data are discussed. The data presented suggest that vaccination protocols should aim to elicit vigorous cytotoxic T lymphocyte responses to HIV-1. Attempts to stimulate polyvalent responses to mutationally intolerant epitopes are likely to be most effective. Optimal management of HIV-1 infection requires an understanding of dynamic host–virus interactions, and may involve strategies designed to enhance cytotoxic T lymphocyte activity following periods of anti-retroviral drug therapy.

scholarly journals Levels of Human Immunodeficiency Virus Type 1-Specific Cytotoxic T-Lymphocyte Effector and Memory Responses Decline after Suppression of Viremia with Highly Active Antiretroviral Therapy

1999 ◽  
Vol 73 (8) ◽  
pp. 6721-6728 ◽  
Author(s):  
Spyros A. Kalams ◽  
Philip J. Goulder ◽  
Amy K. Shea ◽  
Norman G. Jones ◽  
Alicja K. Trocha ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Immune Responses ◽  
T Lymphocyte ◽  
Highly Active Antiretroviral Therapy ◽  
Cytotoxic T Lymphocyte ◽  
Highly Active ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Therapeutic suppression of human immunodeficiency virus type 1 (HIV-1) replication may help elucidate interactions between the host cellular immune responses and HIV-1 infection. We performed a detailed longitudinal evaluation of two subjects before and after the start of highly active antiretroviral therapy (HAART). Both subjects had evidence of in vivo-activated and memory cytotoxic T-lymphocyte precursor (CTLp) activity against multiple HIV-1 gene products. After the start of therapy, both subjects had declines in the levels of in vivo-activated HIV-1-specific CTLs and had immediate increases in circulating HIV-1-specific CTL memory cells. With continued therapy, and continued suppression of viral load, levels of memory CTLps declined. HLA A*0201 peptide tetramer staining demonstrated that declining levels of in vivo-activated CTL activity were associated with a decrease in the expression of the CD38+ activation marker. Transient increases in viral load during continued therapy were associated with increases in the levels of virus-specific CTLps in both individuals. The results were confirmed by measuring CTL responses to discrete optimal epitopes. These studies illustrate the dynamic equilibrium between the host immune response and levels of viral antigen burden and suggest that efforts to augment HIV-1-specific immune responses in subjects on HAART may decrease the incidence of virologic relapse.

In vivo persistence of a HIV-1-encoded HLA-B27-restricted cytotoxic T lymphocyte epitope despite specificin vitro reactivity

1991 ◽  
Vol 21 (10) ◽  
pp. 2637-2640 ◽  
Author(s):  
Andreas Meyerhans ◽  
Gilles Dadaglio ◽  
Jean-Pierre Vartanian ◽  
Pierre Langlade-Demoyen ◽  
Ronald Frank ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Hla B27 ◽  
Hiv 1

Synthesis and evaluation of novel lipopeptide constructs for in vivo induction of virus-specific cytotoxic T-lymphocyte mediated response

Peptides ◽  
1994 ◽  
pp. 736-737 ◽  
Author(s):  
B. Déprez ◽  
H. Gras-Masse ◽  
F. Martinon ◽  
E. Gomard ◽  
J. P. Lévy ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
In Vivo Induction
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