Activation of virus‐specific major histocompatibility complex class II‐restricted CD8<sup>+</sup> cytotoxic T cells in CD4‐deficient mice

Heemskerk, Mirjam H.M.; Schilham, Marco W.; Schoemaker, H.M.; Spierenburg, Gerrit; Spaan, Willy J. M.; Boog, Claire J. P.

doi:10.1002/eji.1830250438

Cited by 16 publications

(17 citation statements)

References 23 publications

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“…1C) (21). Moreover, after infection with various pathogens, CD4 Ϫ/Ϫ mice produce CD8 ϩ T cells that react specifically with strong pMHC-II agonists (50,51). Similarly, CD4 ϩ 2C T cells respond to a potent pMHC-I agonist (QL9-L d ) for the 2C TCR (5).…”

Section: Discussionmentioning

confidence: 99%

Stage-dependent reactivity of thymocytes to self-peptide–MHC complexes

Leng

Nguyen

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Section: Discussionmentioning

confidence: 99%

Stage-dependent reactivity of thymocytes to self-peptide–MHC complexes

Leng

Nguyen

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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“…Previous studies have shown the existence of MHCII-restricted DN and CD8 ϩ T cells after L. major and MHV infection of CD4 Ϫ/Ϫ mice, respectively (14,17). However, the Ag specificities of these MHCII-restricted T cells have not been defined, and their responses are very low, requiring secondary in vitro expansion for their detection and analysis.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, studies using MHCII-restricted TCR transgenic mice to investigate thymic selection have shown that in the absence of CD4, MHCII-restricted T cells are misdirected into the CD8 lineage (16). Consistent with this, MHCII-restricted CD8 ϩ CTLs have been observed in secondary bulk cultures of splenocytes from CD4 Ϫ/Ϫ mice that have been infected with mouse hepatitis virus (MHV) (17). However, in both the L. major and MHV systems, the Ag specificities of MHCII-restricted T cells are not defined, and their responses are very low, requiring secondary in vitro expansion for their detection and analysis.…”

Section: D4mentioning

confidence: 96%

Functional Characterization of MHC Class II-Restricted CD8+CD4− and CD8−CD4− T Cell Responses to Infection in CD4−/− Mice

Pearce

Shedlock

Shen

2004

The Journal of Immunology

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Classical CD4+ and CD8+ T cells recognize Ag presented by MHC class II (MHCII) and MHC class I (MHCI), respectively. However, our results show that CD4−/− mice mount a strong, readily detectable CD8+ T cell response to MHCII-restricted epitopes after a primary bacterial or viral infection. These MHCII-restricted CD8+CD4− T cells are more similar to classical CD8+ T cells than to CD4+ T cells in their expression of effector functions during a primary infection, yet they also differ from MHCI-restricted CD8+ T cells by their inability to produce high levels of the cytolytic molecule granzyme B. After resolution of a primary infection, epitope-specific MHCII-restricted T cells in CD4−/− mice persist for a long period of time as memory T cells. Surprisingly, upon reinfection the secondary MHCII-restricted response in CD4−/− mice consists mainly of CD8−CD4− T cells. In contrast to CD8+ T cells, MHCII-restricted CD8−CD4− T cells are capable of producing IL-2 in addition to IFN-γ and thus appear to have attributes characteristic of CD4+ T cells rather than CD8+ T cells. Therefore, MHCII-restricted T cells in CD4−/− mice do not share all phenotypic and functional characteristics with MHCI-restricted CD8+ T cells or with MHCII-restricted CD4+ T cells, but, rather, adopt attributes from each of these subsets. These results have implications for understanding thymic T cell selection and for elucidating the mechanisms regulating the peripheral immune response and memory differentiation.

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“…In addition, several cytotoxic T lymphocyte lines and clones of the CD8 phenotype exhibiting class II restricted reactivity (30)(31)(32) and alloreactive CD4 ϩ T cells exhibiting a class I-restricted proliferative capacity have been described (33). Based on the assumption that during T cell development CD8 ϩ T cells are selected on HLA class I and CD4 ϩ T cells on HLA class II, we hypothesize that these previously described T cells also have a specificity recognizing a peptide in the MHC for which they are selected.…”

Section: Discussionmentioning

confidence: 99%

Dual HLA class I and class II restricted recognition of alloreactive T lymphocytes mediated by a single T cell receptor complex

Heemskerk

Paus

Lurvink

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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The alloreactive human T cell clone MBM15 was found to exhibit dual specificity recognizing both an antigen in the context of the HLA class I A2 molecule and an antigen in the context of the HLA class II DR1. We demonstrated that the dual reactivity that was mediated via a single clonal T cell population depended on specific peptide binding. For complete recognition of the HLA-A2-restricted specificity the interaction of CD8 with HLA class I is essential. Interestingly, interaction of the CD8 molecule with HLA class I contributed to the HLA-DR1-restricted specificity. T cell clone MBM15 expressed two in-frame T cell receptor (TCR) V␣ transcripts (V␣1 and V␣2) and one TCR V␤ transcript (V␤13). To elucidate whether two TCR complexes were responsible for the dual recognition or one complex, cytotoxic T cells were transduced with retroviral vectors encoding the different TCR chains. Only T cells transduced with the TCR V␣1V␤13 combination specifically recognized both the HLA-A2 ؉ and HLA-DR1 ؉ target cells, whereas the V␣2V␤13 combination did not result in a TCR on the cell surface. T he function of the major histocompatibility complex (MHC) molecules is to bind and display peptides to T lymphocytes. Allogeneic MHC molecules can induce strong T cell responses, which is reflected by the mixed lymphocyte reaction in vitro and the high incidence of graft rejection and graft versus host disease after transplantation of organs or hematopoietic cells over MHC barriers. T cell recognition of allogeneic MHC is often peptide specific, resembling self-MHC-restricted T cell recognition of foreign antigens (1-3). However, alloreactive T cells are heterogeneous in their degree of peptide specificity (4), and a minor population might be peptide independent or recognize motifs shared by many peptides (5). Several alloreactive T cell clones have been described to be crossreactive, recognizing two unrelated peptides in the context of two different allogeneic MHC class I molecules (6, 7). In addition, alloreactive cytotoxic T lymphocytes recognizing an endogenously processed peptide binding to allogeneic MHC molecules and recognizing a different peptide in the context of self-MHC class I have been described (8). In one instance, crossreactive cytotoxic T lymphocytes showing dual recognition for both HLA class I and class II molecules also have been reported (9, 10). Those authors postulated that based on the shared structural motif between the HLA-B27 and the DR2 B5*0101 chain, the reactivity pattern reflected presentation of identical or structurally related peptides by HLA-B27 and HLA-DR2. In several of these previously mentioned studies, cold-target inhibition experiments were performed to confirm that one clonal T cell population was mediating the crossreactivity. However, whether the crossreactivity of these alloreactive T cell clones was mediated via one or two T cell receptor (TCR) ␣␤ complexes was not investigated. This hypothesis may be possible because 20% of peripheral human T cells and 10% of mouse T cells express two dif...

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Activation of virus‐specific major histocompatibility complex class II‐restricted CD8⁺ cytotoxic T cells in CD4‐deficient mice

Cited by 16 publications

References 23 publications

Stage-dependent reactivity of thymocytes to self-peptide–MHC complexes

Stage-dependent reactivity of thymocytes to self-peptide–MHC complexes

Functional Characterization of MHC Class II-Restricted CD8+CD4− and CD8−CD4− T Cell Responses to Infection in CD4−/− Mice

Dual HLA class I and class II restricted recognition of alloreactive T lymphocytes mediated by a single T cell receptor complex

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Activation of virus‐specific major histocompatibility complex class II‐restricted CD8+ cytotoxic T cells in CD4‐deficient mice

Cited by 16 publications

References 23 publications

Stage-dependent reactivity of thymocytes to self-peptide–MHC complexes

Stage-dependent reactivity of thymocytes to self-peptide–MHC complexes

Functional Characterization of MHC Class II-Restricted CD8+CD4− and CD8−CD4− T Cell Responses to Infection in CD4−/− Mice

Dual HLA class I and class II restricted recognition of alloreactive T lymphocytes mediated by a single T cell receptor complex

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Activation of virus‐specific major histocompatibility complex class II‐restricted CD8⁺ cytotoxic T cells in CD4‐deficient mice