On cross-priming of MHC class I-specific CTL: rule or exception?

Zinkernagel, Rolf M.

doi:10.1002/1521-4141(200209)32:9<2385::aid-immu2385>3.0.co;2-v

Cited by 128 publications

(89 citation statements)

References 65 publications

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“…This investigation is particularly pertinent given the ongoing debate about the physiological relevance of cross-versus direct-presentation. Specifically, despite evidence of a role for cross-presentation from an ever-increasing number of experimental systems in both T CD81 priming and tolerance induction [14,26,27], Zinkernagel has argued that cross-presentation is of too low efficiency to be important under normal circumstances, since non-physiological conditions are typically employed to observe its effects [17].…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…However, the importance of cross-presentation in physiological situations has been questioned. Zinkernagel has argued that although cross-presentation can be demonstrated in model systems, the requirements for high antigen concentration, non-physiological methods of cytosolic loading, and the use of high numbers of Tg reporter T CD81 means that these findings may not necessarily reflect physiological conditions in vivo [16,17].We have examined which Ag presentation pathway, direct-or cross-presentation, is active in selecting the T CD81 repertoire specific to the nuclear antigen La using a mouse model. La is a ubiquitous nuclear protein involved in the termination of RNA polymerase III transcripts, and is found stably associated in the Ro/La ribonucleoprotein complex [18].…”

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confidence: 99%

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Direct antigen presentation by DC shapes the functional CD8⁺ T‐cell repertoire against the nuclear self‐antigen La‐SSB

et al. 2010

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Controversy still surrounds the importance of cross-presentation versus endogenous or direct presentation of MHC-I restricted Ag in CD8 1 T-cell (T CD81 ) immunity. It is even less clear what relative role these pathways play in shaping the T-cell repertoire specific for ubiquitous self-antigens, especially in cases where both Ag presentation pathways could potentially be involved. Here we provide evidence that a T CD81 repertoire specific for a determinant from the nuclear autoantigen La-SSB is largely shaped by direct presentation. In this system, mouse T CD81 reactive to a xenogeneic human La (hLa [51][52][53][54][55][56][57][58] ) K b peptide did not recognize directly presented peptide on either spleen cells from hLa-Tg mice or hLa transfected syngeneic cells. Interestingly, the same T CD81 were activated by in vivo challenge with allogeneic APC expressing either the Tg hLa or loaded with intact recombinant hLa protein, indicating functional cross-presentation of the hLa [51][52][53][54][55][56][57][58] . However, in irradiated bone marrow chimeric mice, DC expressing Tg hLa, but not WT DC that matured in hLa-Tg mice, constitutively presented the hLa [51][52][53][54][55][56][57][58] to T CD81 . These data demonstrate that although both the direct-and cross-presentation pathways are potentially operative in revealing hLa [51][52][53][54][55][56][57][58] to T CD81 , the T CD81 repertoire to this determinant is shaped quantitatively according to the efficiency of Ag presentation.Key words: Antigen processing/presentation . Autoimmunity . T-cell repertoire IntroductionAutoimmunity to nuclear antigens, in particular components of ribonucleoprotein complexes, is common in systemic autoimmune syndromes such as systemic lupus erythematosus and primary Sjögren's syndrome [1]. However, the mechanisms that shape the T-cell repertoire to these proteins and the role these auto-reactive T cells play in disease pathology are not well understood. Poor self-tolerance of some nuclear/cytoplasmic proteins and a propensity for them to become autoimmune targets could result from their sequestered localization [2], their low abundance or rapid turnover [3], and their exposure to antibodies during redistribution and concentration in apoptotic blebs [4]. Further, their association with RNA and the potential to stimulate TLR7 and 8 [5], coupled with defects in apoptosis and clearance of debris, renders some nuclear Ag as clinically relevant targets of autoimmunity [6,7]. Although much of the pathology in systemic autoimmunity is due to the deposition of complement-fixing immune complexes [8], CD81 T cells (T CD81 ) have increasingly been implicated in other autoimmune conditions [9,10]. However, the functional T CD81 repertoire specific to such nuclear autoantigens and the mode of MHC-I restricted antigen 330presentation (direct-versus cross-presentation) during the establishment of such T CD81 repertoire have not been investigated.The T CD81 repertoire is shaped by MHC-I restricted antigens presented on APC both in the thymus and...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Direct antigen presentation by DC shapes the functional CD8⁺ T‐cell repertoire against the nuclear self‐antigen La‐SSB

et al. 2010

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“…It has been argued that the importance of cross-priming of CTL responses has been overemphasized [1]. Crosspriming implies that nucleated cells, e.g.…”

Section: Introductionmentioning

confidence: 99%

“…infected non-professional APC can directly prime CTL against certain epitopes of LCMV (reviewed in [1,2]), it is not excluded that host DC are involved in the priming. Signals from ligands of Toll-like receptors (TLR) or other powerful inflammatory signals generated by the LCMV infection may cause marked DC activation.…”

Section: Introductionmentioning

confidence: 99%

Mini‐review: Regulation of cytotoxic T lymphocyte responses by dendritic cells: peaceful coexistence of cross‐priming and direct priming?

2003

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Cross-priming is the process whereby professional APC, mainly dendritic cells (DC), prime T cells by presenting antigens processed from proteins of other cells such as tumor cells or virus-infected cells. It has been argued that the importance of cross-priming of CD8 + CTL responses has been overemphasized, despite strong evidence that these mechanisms operate when infectious organisms, tumors or self antigens cannot efficiently access the biosynthetic MHC class I processing pathway of DC. Since DC are ideally equipped to capture exogenous antigen and also, particularly in the mature state, express costimulatory molecules, it is difficult to distinguish whether effects are due to cross-presentation, costimulation, or both. Whether cross-priming or cross-tolerance occurs depends on the maturation state of the DC, as well as the levels of MHC class I-bound peptides they present. Crosspresentation of tumor-derived antigens has been demonstrated but, importantly, requires adequate APC activation to prime CTL responses. Similarly, cross-presentation of antigens from infectious organisms appears to be common, and frequently leads to cross-priming. Interactions between cross-presenting DC, CD4 + cells and CD8 + T cells in the establishment of immunological memory are still not well defined. Experiments utilizing DC depletion are needed to further examine the role of processes such as cross-priming and costimulation in the immune response.

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Crossprocessing and Crosspresentation

Škoberne¹,

Bhardwaj²

2006

Handbook of Dendritic Cells

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On cross-priming of MHC class I-specific CTL: rule or exception?

Cited by 128 publications

References 65 publications

Direct antigen presentation by DC shapes the functional CD8⁺ T‐cell repertoire against the nuclear self‐antigen La‐SSB

Direct antigen presentation by DC shapes the functional CD8⁺ T‐cell repertoire against the nuclear self‐antigen La‐SSB

Mini‐review: Regulation of cytotoxic T lymphocyte responses by dendritic cells: peaceful coexistence of cross‐priming and direct priming?

Crossprocessing and Crosspresentation

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On cross-priming of MHC class I-specific CTL: rule or exception?

Cited by 128 publications

References 65 publications

Direct antigen presentation by DC shapes the functional CD8+ T‐cell repertoire against the nuclear self‐antigen La‐SSB

Direct antigen presentation by DC shapes the functional CD8+ T‐cell repertoire against the nuclear self‐antigen La‐SSB

Mini‐review: Regulation of cytotoxic T lymphocyte responses by dendritic cells: peaceful coexistence of cross‐priming and direct priming?

Crossprocessing and Crosspresentation

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Direct antigen presentation by DC shapes the functional CD8⁺ T‐cell repertoire against the nuclear self‐antigen La‐SSB

Direct antigen presentation by DC shapes the functional CD8⁺ T‐cell repertoire against the nuclear self‐antigen La‐SSB