Characterization of Cross-Reactive CD8
            <sup>+</sup>
            T-Cell Recognition of HLA-A2-Restricted HIV-Gag (SLYNTVATL) and HCV-NS5b (ALYDVVSKL) Epitopes in Individuals Infected with Human Immunodeficiency and Hepatitis C Viruses

Vali, Bahareh; Tohn, Robert; Cohen, Michael J.; Sakhdari, Ali; Sheth, Prameet M.; Yue, Feng Yun; Wong, David; Kovacs, Colin; Kaul, Rupert; Ostrowski, Mario

doi:10.1128/jvi.01743-10

Cited by 18 publications

(14 citation statements)

References 25 publications

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“…In contrast, there is less known about the role of heterologous immunity in the induction and maintenance of HIV-specific CD8 + T cell responses. Several studies have shown that cross reactivity between the HIV-1 SL9 peptide and the immunodominant influenza peptide GL9 [ 23 – 24 ] or the HCV peptide AL9 [ 25 ] can occur in HIV-infected HLA-A2 + subjects. Additionally, several studies have looked at the ability of the TCR to cross-react to escape variants within HIV epitopes [ 26 – 30 ].…”

Section: Discussionmentioning

confidence: 99%

Cross-reactive microbial peptides can modulate HIV-specific CD8+ T cell responses

et al. 2018

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Heterologous immunity is an important aspect of the adaptive immune response. We hypothesized that this process could modulate the HIV-1-specific CD8+ T cell response, which has been shown to play an important role in HIV-1 immunity and control. We found that stimulation of peripheral blood mononuclear cells (PBMCs) from HIV-1-positive subjects with microbial peptides that were cross-reactive with immunodominant HIV-1 epitopes resulted in dramatic expansion of HIV-1-specific CD8+ T cells. Interestingly, the TCR repertoire of HIV-1-specific CD8+ T cells generated by ex vivo stimulation of PBMCs using HIV-1 peptide was different from that of cells stimulated with cross-reactive microbial peptides in some HIV-1-positive subjects. Despite these differences, CD8+ T cells stimulated with either HIV-1 or cross-reactive peptides effectively suppressed HIV-1 replication in autologous CD4+ T cells. These data suggest that exposure to cross-reactive microbial antigens can modulate HIV-1-specific immunity.

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Section: Discussionmentioning

confidence: 99%

Cross-reactive microbial peptides can modulate HIV-specific CD8+ T cell responses

et al. 2018

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“…Examples of such cross-reactivity include HIV and human cytomegalovirus (CMV), 73 HIV and Influenza A, 74 Influenza A and EBV, 75,76 Influenza A and HCV, 77–79 and HCV and human herpes virus (HHV1). 80 …”

Section: Immunology Of T Cell Cross-reactivitymentioning

confidence: 99%

“…63,67,70,73,74,77,78 Estimates of cross-reactivity of known clones can be up to 10 6 different peptides. 6,72 At the same time, several reports have indicated an extremely low frequency of cross-reactions between unrelated peptides.…”

Section: Immunology Of T Cell Cross-reactivitymentioning

confidence: 99%

Cross-Reactivity of T Cells and Its Role in the Immune System

2012

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T-cell receptors recognize peptides presented by the major histocompatibility complex (MHC) on the surface of antigen-presenting cells (APC). The ability of the T-cell receptor (TCR) to recognize more than one peptide-MHC structure defines cross-reactivity. Cross-reactivity is a documented phenomenon of the immune system whose importance is still under investigation. There are a number of rational arguments for cross-reactivity. These include the discrepancy between the theoretical high number of pathogen-derived peptides and the lower diversity of the T-cell repertoire, the need for recognition of escape variants, and the intrinsic low affinity of this receptor–ligand pair. However, quantifying the phenomenon has been difficult, and its immunological importance remains unknown. In this review, we examined the cases for and against an important role for cross reactivity. We argue that it may be an essential feature of the immune system from the point of view of biological robustness.

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“…While numerous studies have examined "cross-reactivity" of HIV-1-specific CTLs against target epitope variation within HIV-1, the degree to which they recognize truly heterologous epitopes is unclear. Limited data have suggested that there can be CTL cross-reactivity with microbial peptides (3), hepatitis C virus (4), and a self-protein (5). Here, we find unexpectedly that HIV-1-specific CTLs commonly exhibit cross-reactivity against epitopes from other regions of the HIV-1 proteome.…”

mentioning

confidence: 52%

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

Balamurugan

Yang

2018

J Virol

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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. 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.

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Characterization of Cross-Reactive CD8 ⁺ T-Cell Recognition of HLA-A2-Restricted HIV-Gag (SLYNTVATL) and HCV-NS5b (ALYDVVSKL) Epitopes in Individuals Infected with Human Immunodeficiency and Hepatitis C Viruses

Cited by 18 publications

References 25 publications

Cross-reactive microbial peptides can modulate HIV-specific CD8+ T cell responses

Cross-reactive microbial peptides can modulate HIV-specific CD8+ T cell responses

Cross-Reactivity of T Cells and Its Role in the Immune System

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

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Characterization of Cross-Reactive CD8 + T-Cell Recognition of HLA-A2-Restricted HIV-Gag (SLYNTVATL) and HCV-NS5b (ALYDVVSKL) Epitopes in Individuals Infected with Human Immunodeficiency and Hepatitis C Viruses

Cited by 18 publications

References 25 publications

Cross-reactive microbial peptides can modulate HIV-specific CD8+ T cell responses

Cross-reactive microbial peptides can modulate HIV-specific CD8+ T cell responses

Cross-Reactivity of T Cells and Its Role in the Immune System

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

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Product

Resources

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Characterization of Cross-Reactive CD8 ⁺ T-Cell Recognition of HLA-A2-Restricted HIV-Gag (SLYNTVATL) and HCV-NS5b (ALYDVVSKL) Epitopes in Individuals Infected with Human Immunodeficiency and Hepatitis C Viruses