Cross-presentation: a general mechanism for CTL immunity and tolerance

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Abstract

MHC class I-restricted presentation is usually associated with the processing of endogenous antigens. However, this restriction element can present antigens that do not originate within the presenting cells. Here, Francis Carbone and colleagues describe how such cross-presentation is critical for cytotoxic T-cell surveillance of peripheral antigens, both self and foreign, located outside the secondary lymphoid compartment.

Section snippets

A mechanism for directing peripheral antigen into the MHC class I presentation pathway

Most studies showing exclusion of exogenous antigen from the class I presentation pathway have used the favourite tools of the cellular immunologist, notably, fully activated effector T cells and established tumour-cell lines to present the target antigen3, 4. These reagents mimic the physiological situation where armed and migrating effector CTLs lyse virus-infected target cells, but they do not address the nature of antigen presentation during the priming phase of the immune response. Such

Cross-presentation is involved in CD8+ T-cell deletion

Cross-presentation of exogenous antigen was originally described in the context of T-cell priming, but there is also evidence that a similar presentation mechanism can contribute to T-cell tolerance18, 19. von Boehmer and Hafen[18]showed that maturing CD8+ T cells could be tolerized to minor histocompatibility antigens expressed on thymic epithelial cells, even when such cells did not carry the correct restricting MHC class I elements. In this case the antigen was presented by APCs most likely

CD4+ T-cell involvement can determine the choice between cross-priming and cross-tolerance

Antigen-specific CD4+ Th cells are important contributors to effective CTL priming. It is established that many, although clearly not all, CTL responses require the active involvement of CD4+ T cells25, 26, 27. However, the basis for this requirement has largely remained obscure. The contribution of Th cells to humoral immune responses is elegantly explained by a cognate interaction involving the B-cell-expressed MHC class II molecules and antigen-specific CD4+ T cells, often with the active

Identity of the cross-presenting APC and access to the MHC class I presentation pathway

The identity of the cross-presenting APC and the means by which it can direct the class I-restricted presentation of exogenous antigens remains controversial. In addition, we have little idea where the APCs capture their antigenic cargo: in the tissues where the antigen is expressed or the lymph nodes where the presentation actually takes place.

There are a number of mechanisms which appear to provide exogenous antigens access to the MHC class I-restricted presentation pathway. For example, in

The physiological role for cross-priming

We have purposely focused our discussion on the CTL response to antigens expressed in locations outside the secondary lymphoid organs. In this situation (Fig. 3), the cross-presentation mechanism permits the co-localization of antigen, professional APCs, Th cells and CTLs in a central location, notably the lymph nodes that drain sites of peripheral antigen expression. As Bevan suggested, this pathway may be critical for responses to tissue-tropic viruses[11], but is this the only purpose of

Acknowledgements

The authors wish to thank P. Gleeson and members of the Carbone and Heath laboratories for helpful comments.

References (64)

  • M.W. Moore et al.

    Cell

    (1988)
  • J.P. Allison

    Curr. Opin. Immunol.

    (1994)
  • C.R. Mackay

    Immunol. Today

    (1991)
  • P.S. Ohashi et al.

    Cell

    (1991)
  • M.B. Oldstone et al.

    Cell

    (1991)
  • C.C. Norbury et al.

    Immunity

    (1995)
  • P. Brossart et al.

    Blood

    (1997)
  • A.Y.C. Huang et al.

    Immunity

    (1996)
  • R.N. Germain et al.

    Annu. Rev. Immunol.

    (1993)
  • I.A. York et al.

    Annu. Rev. Immunol.

    (1996)
  • J.W. Yewdell et al.

    Science

    (1988)
  • F.A. Harding et al.

    J. Exp. Med.

    (1993)
  • E.C. Butcher et al.

    Science

    (1996)
  • M.J. Bevan

    J. Exp. Med.

    (1976)
  • R.B. Gordon et al.

    J. Exp. Med.

    (1976)
  • M.J. Bevan

    Nature

    (1987)
  • F.R. Carbone et al.

    J. Exp. Med.

    (1990)
  • M.F. Bachmann et al.

    Eur. J. Immunol.

    (1994)
  • M. Kovacsovic-Bankowski et al.

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

    (1993)
  • C.V. Harding et al.

    J. Immunol.

    (1994)
  • K. Speidel et al.

    Eur. J. Immunol.

    (1997)
  • C. Kurts et al.

    J. Exp. Med.

    (1996)
  • H. von Boehmer et al.

    Nature

    (1986)
  • C. Kurts et al.

    J. Exp. Med.

    (1997)
  • D. Lo et al.

    Eur. J. Immunol.

    (1992)
  • Kurts, C., Miller, J.F.A.P., Subrumaniam, R.M., Carbone, F.R. and Heath, W.R. J. Exp. Med. (in...
  • R.W. Tindle et al.

    Curr. Top. Microbiol. Immunol.

    (1994)
  • J.A. Keene et al.

    J. Exp. Med.

    (1982)
  • L.A. Husmann et al.

    Ann. New York Acad. Sci.

    (1988)
  • R.D. Cardin et al.

    J. Exp. Med.

    (1996)
  • A. Lanzavecchia

    Nature

    (1985)
  • S.R.M. Bennett et al.

    J. Exp. Med.

    (1997)
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