scholarly journals Cross-Reactivity against Multiple HIV-1 Epitopes Is Characteristic of HIV-1-Specific Cytotoxic T Lymphocyte Clones

2018 ◽  
Vol 92 (16) ◽  
Author(s):  
Arumugam Balamurugan ◽  
Hwee L. Ng ◽  
Otto O. Yang
Keyword(s):  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Cross Reactivity ◽  
Type I ◽  
Mhc I ◽  
Infected Cells ◽  
High Concentrations ◽  
High Level ◽  
Hiv 1 ◽  
Ctl Responses

ABSTRACT Although a high level of promiscuity for heterologous epitopes is believed to exist for cellular immunity, limited data explore this issue for human immunodeficiency virus type 1 (HIV-1)-specific CD8+ T lymphocyte (CTL) responses. Here, we found an unexpected degree of heterologous cross-reactivity against HIV-1 epitopes, in addition to the targeted index epitope. Most CTL clones screened cross-reacted against other known HIV-1 epitopes of the same major histocompatibility complex type I (MHC-I) restriction, up to 40% of tested nonindex epitopes in some cases. The observed cross-reactivity was universally lower avidity than recognition of the index epitope when examined for several A*02- and B*57-restricted CTL clones, demonstrating that the high concentrations of exogenous epitope typically used for screening of CTL responses are prone to detect such cross-reactivity spuriously. In agreement with this, we found that these cross-reactive responses do not appear to mediate CTL activity against HIV-1-infected cells. Overall, our data indicate that low-level cross-reactivity is remarkably common for HIV-1-specific CTLs. The role of this phenomenon is unclear, but low-avidity interactions have been shown to foster homeostatic proliferation of memory T cells. IMPORTANCE This study raises two issues related to HIV-1-specific CTL responses. These are key immune responses that retard disease progression in infected persons that are highly relevant to immunotherapies and vaccines for HIV-1. First, we make the novel observation that these responses are promiscuous and that CTLs targeting one epitope may cross-recognize other, completely distinct epitopes in the virus. While these are low-avidity interactions that do not appear to contribute directly to the antiviral activity of CTLs, this raises interesting biologic implications regarding the purpose of the phenomenon, such as providing a stimulus for these responses to persist long term. Second, the data raise a technical caveat to detection of CTL responses against particular epitopes, suggesting that some methodologies may unintentionally detect cross-reactivity and overestimate responses against an epitope.

HIV-1-Specific Cytotoxic T Lymphocyte (CTL) Responses Against Immunodominant Optimal Epitopes Slow the Progression of AIDS in China

2008 ◽  
Vol 6 (4) ◽  
pp. 335-350 ◽  
Author(s):  
Song Zhai ◽  
Yan Zhuang ◽  
Yang Song ◽  
Shu Li ◽  
Dedong Huang ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Hiv 1 ◽  
Ctl Responses

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

scholarly journals Identification of Dominant Optimal HLA-B60- and HLA-B61-Restricted Cytotoxic T-Lymphocyte (CTL) Epitopes: Rapid Characterization of CTL Responses by Enzyme-Linked Immunospot Assay

2000 ◽  
Vol 74 (18) ◽  
pp. 8541-8549 ◽  
Author(s):  
Marcus A. Altfeld ◽  
Alicja Trocha ◽  
Robert L. Eldridge ◽  
Eric S. Rosenberg ◽  
Mary N. Phillips ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Mononuclear Cells ◽  
Cytotoxic T Lymphocyte ◽  
Hla Class I ◽  
Peripheral Blood Mononuclear ◽  
Antiviral Immune Response ◽  
Ctl Epitopes ◽  
Hla Class I Molecules ◽  
Hiv 1 ◽  
Ctl Responses

ABSTRACT Human immunodeficiency virus type 1 (HIV-1)-specific cytotoxic T-lymphocyte (CTL) responses play a major role in the antiviral immune response, but the relative contribution of CTL responses restricted by different HLA class I molecules is less well defined. HLA-B60 or the related allele B61 is expressed in 10 to 20% of Caucasoid populations and is even more highly prevalent in Asian populations, but yet no CTL epitopes restricted by these alleles have been defined. Here we report the definition of five novel HLA-B60-restricted HIV-1-specific CTL epitopes, using peripheral blood mononuclear cells in enzyme-linked immunospot (Elispot) assays and using CTL clones and lines in cytolytic assays. The dominant HLA-B60-restricted epitope, Nef peptide KEKGGLEGL, was targeted by all eight subjects with B60 and also by both subjects with B61 studied. This study additionally establishes the utility of the Elispot assay as a more rapid and efficient method of defining novel CTL epitopes. This approach will help to define new CTL epitopes that may play an important role in the immune control of HIV-1.

scholarly journals Major Histocompatibility Complex Class I Alleles Associated with Slow Simian Immunodeficiency Virus Disease Progression Bind Epitopes Recognized by Dominant Acute-Phase Cytotoxic-T-Lymphocyte Responses

2003 ◽  
Vol 77 (16) ◽  
pp. 9029-9040 ◽  
Author(s):  
David H. O'Connor ◽  
Bianca R. Mothe ◽  
Jason T. Weinfurter ◽  
Sarah Fuenger ◽  
William M. Rehrauer ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Disease Progression ◽  
Acute Phase ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Complex Class ◽  
Mhc I ◽  
Histocompatibility Complex ◽  
Immunodeficiency Virus ◽  
Ctl Responses

ABSTRACT Certain major histocompatibility complex class I (MHC-I) alleles are associated with delayed disease progression in individuals infected with human immunodeficiency virus (HIV) and in macaques infected with simian immunodeficiency virus (SIV). However, little is known about the influence of these MHC alleles on acute-phase cellular immune responses. Here we follow 51 animals infected with SIVmac239 and demonstrate a dramatic association between Mamu-A*01 and -B*17 expression and slowed disease progression. We show that the dominant acute-phase cytotoxic T lymphocyte (CTL) responses in animals expressing these alleles are largely directed against two epitopes restricted by Mamu-A*01 and one epitope restricted by Mamu-B*17. One Mamu-A*01-restricted response (Tat28-35SL8) and the Mamu-B*17-restricted response (Nef165-173IW9) typically select for viral escape variants in early SIVmac239 infection. Interestingly, animals expressing Mamu-A*1 and -B*17 have less variation in the Tat28-35SL8 epitope during chronic infection than animals that express only Mamu-A*01. Our results show that MHC-I alleles that are associated with slow progression to AIDS bind epitopes recognized by dominant CTL responses during acute infection and underscore the importance of understanding CTL responses during primary HIV infection.

scholarly journals Elicitation of High-Frequency Cytotoxic T-Lymphocyte Responses against both Dominant and Subdominant Simian-Human Immunodeficiency Virus Epitopes by DNA Vaccination of Rhesus Monkeys

2001 ◽  
Vol 75 (5) ◽  
pp. 2462-2467 ◽  
Author(s):  
Dan H. Barouch ◽  
Abie Craiu ◽  
Sampa Santra ◽  
Michael A. Egan ◽  
Jörn E. Schmitz ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Lymphocyte ◽  
Plasmid Dna ◽  
High Frequency ◽  
Rhesus Monkeys ◽  
Cytotoxic T Lymphocyte ◽  
Ctl Response ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Ctl Responses

ABSTRACT Increasing evidence suggests that the generation of cytotoxic T-lymphocyte (CTL) responses specific for a diversity of viral epitopes will be needed for an effective human immunodeficiency virus type 1 (HIV-1) vaccine. Here, we determine the frequencies of CTL responses specific for the simian immunodeficiency virus Gag p11C and HIV-1 Env p41A epitopes in simian-human immunodeficiency virus (SHIV)-infected and vaccinated rhesus monkeys. The p11C-specific CTL response was high frequency and dominant and the p41A-specific CTL response was low frequency and subdominant in both SHIV-infected monkeys and in monkeys vaccinated with recombinant modified vaccinia virus Ankara vectors expressing these viral antigens. Interestingly, we found that plasmid DNA vaccination led to high-frequency CTL responses specific for both of these epitopes. These data demonstrate that plasmid DNA may be useful in eliciting a broad CTL response against multiple epitopes.

Cytotoxic T lymphocyte recognition of HLA-B*5101-restricted HIV-1 Rev epitope which is naturally processed in HIV-1-infected cells

AIDS ◽  
1999 ◽  
Vol 13 (7) ◽  
pp. 861 ◽  
Author(s):  
Hiroko Tomiyama ◽  
Yoshitomo Chujoh ◽  
Tatsuo Shioda ◽  
Kiyoshi Miwa ◽  
Shin-ichi Oka ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Infected Cells ◽  
Hiv 1

Cytotoxic T-Lymphocyte (CTL) Responses Directed against Regulatory and Accessory Proteins in HIV-1 Infection

2002 ◽  
Vol 21 (9) ◽  
pp. 671-678 ◽  
Author(s):  
M.M. Addo ◽  
X.G. Yu ◽  
E.S. Rosenberg ◽  
B.D. Walker ◽  
M. Altfeld
Keyword(s):  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Accessory Proteins ◽  
Hiv 1 ◽  
Ctl Responses

scholarly journals Immune Screening Identifies Novel T Cell Targets Encoded by Antisense Reading Frames of HIV-1

2015 ◽  
Vol 89 (7) ◽  
pp. 4015-4019 ◽  
Author(s):  
Christoph T. Berger ◽  
Anuska Llano ◽  
Jonathan M. Carlson ◽  
Zabrina L. Brumme ◽  
Mark A. Brockman ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocyte ◽  
Cellular Immunity ◽  
Cytotoxic T Lymphocyte ◽  
Sequence Alignments ◽  
Computational Approaches ◽  
Anti Hiv ◽  
Reading Frames ◽  
Hiv 1 ◽  
Ctl Responses

Cytotoxic-T lymphocyte (CTL) responses to epitopes in alternative HIV reading frames have been reported. However, the extent of CTL responses to putative proteins encoded in antisense reading frames is unknown. Using sequence alignments and computational approaches, we here predict five potential antisense HIV proteins and characterize common CTL responses against them. Results suggest that antisense-derived sequences are commonly transcribed and translated and could encode functional proteins that contain important targets of anti-HIV cellular immunity.

scholarly journals CD8+Cytotoxic-T-Lymphocyte Breadth Could Facilitate Early Immune Detection of Immunodeficiency Virus-Derived Epitopes with Limited Expression Levels

mSphere ◽  
2019 ◽  
Vol 4 (1) ◽  
Author(s):  
Tetsuo Tsukamoto ◽  
Hiroyuki Yamamoto ◽  
Tetsuro Matano
Keyword(s):  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Physical Contact ◽  
Class I Mhc ◽  
Mhc I ◽  
Expression Levels ◽  
Immunodeficiency Virus ◽  
Infected Cells ◽  
Attenuated Viruses

ABSTRACTCytotoxic-T-lymphocyte (CTL) responses are important to control the replication of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). Accumulating evidence suggests that the ability of a few immunodominant T-cell populations to detect and kill HIV/SIV-infected cells is important in individuals with a protective major histocompatibility complex class I (MHC-I) allele. On the other hand, immunization with live(-attenuated) viruses may be effective against superinfection of virulent viral strains regardless of the host’s MHC-I haplotypes, although the underlying mechanisms have not been fully documented. In this article, we propose a hypothesis that the early detection of infected cells in superinfected individuals may be partly facilitated by recognition of diverse CTL epitopes with limited expression levels. We further explain the hypothesis using simple mathematics that was written based on previousin vitroviral suppression assay results and by considering the physical contact of infected cells with CTLs.

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