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The Specific Regulation Of Immune Responses By CD8 + T Cells Restricted By The MHC Class Ib Molecule, Qa-1

The Specific Regulation Of Immune Responses By CD8 + T Cells Restricted By The MHC Class Ib... Over the last three decades considerable evidence has accumulated that CD8 + T cells regulate peripheral immune responses, in part, by specifically controlling the outgrowth of antigen-triggered CD4 + T cells. This regulatory function of CD8 + T cells has been shown, in vivo, to control the emergence of autoreactive CD4 + T cells as well as CD4 + T cells reactive to conventional antigens, including alloantigens. In this review, we summarize the evidence that this immune suppression mediated by CD8 + T cells is dependent, in part, on specific cognate interactions between MHC class I–restricted regulatory CD8 + cells and antigen-activated CD4 + T cells. Moreover, we review the evidence that regulatory CD8 + T cells recognize antigen-activated CD4 + T cells in a TCR specific manner restricted by the MHC class Ib molecule, Qa-1. The Qa-1 molecule may be uniquely qualified to serve this MHC restrictive function because, unlike conventional MHC molecules, it is preferentially and transiently expressed on activated and not resting CD4 + T cells. This may assure that only recently antigen-activated CD4 + T cells expressing Qa-1/TCR peptide complexes will induce regulatory CD8 + T cells and subsequently become susceptible to regulation. Because Qa-1 also binds to self Qdm peptides that trigger NK (CD94/ NKG2) receptors on CD8 + T cells, the machinery for homeostatic regulation of regulatory CD8 + T cells can be envisioned. Finally, we propose a model by which these TCR specific, Qa-1-restricted regulatory CD8 + T cells selectively downregulate antigen-activated T cells expressing TCRs of certain affinities. Ultimately these regulatory CD8 + T cells control the peripheral TCR repertoire during the course of immune responses to both self and foreign antigens. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Annual Review of Immunology Annual Reviews

The Specific Regulation Of Immune Responses By CD8 + T Cells Restricted By The MHC Class Ib Molecule, Qa-1

Jiang, Hong; Chess, Leonard
Annual Review of Immunology , Volume 18 (1) – Apr 1, 2000
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References (178)

Publisher
Annual Reviews
Copyright
Copyright © by Annual Reviews. All rights reserved
Subject
Review Articles
ISSN
0732-0582
eISSN
1545-3278
DOI
10.1146/annurev.immunol.18.1.185
pmid
10837057
Publisher site
See Article on Publisher Site

Abstract

Over the last three decades considerable evidence has accumulated that CD8 + T cells regulate peripheral immune responses, in part, by specifically controlling the outgrowth of antigen-triggered CD4 + T cells. This regulatory function of CD8 + T cells has been shown, in vivo, to control the emergence of autoreactive CD4 + T cells as well as CD4 + T cells reactive to conventional antigens, including alloantigens. In this review, we summarize the evidence that this immune suppression mediated by CD8 + T cells is dependent, in part, on specific cognate interactions between MHC class I–restricted regulatory CD8 + cells and antigen-activated CD4 + T cells. Moreover, we review the evidence that regulatory CD8 + T cells recognize antigen-activated CD4 + T cells in a TCR specific manner restricted by the MHC class Ib molecule, Qa-1. The Qa-1 molecule may be uniquely qualified to serve this MHC restrictive function because, unlike conventional MHC molecules, it is preferentially and transiently expressed on activated and not resting CD4 + T cells. This may assure that only recently antigen-activated CD4 + T cells expressing Qa-1/TCR peptide complexes will induce regulatory CD8 + T cells and subsequently become susceptible to regulation. Because Qa-1 also binds to self Qdm peptides that trigger NK (CD94/ NKG2) receptors on CD8 + T cells, the machinery for homeostatic regulation of regulatory CD8 + T cells can be envisioned. Finally, we propose a model by which these TCR specific, Qa-1-restricted regulatory CD8 + T cells selectively downregulate antigen-activated T cells expressing TCRs of certain affinities. Ultimately these regulatory CD8 + T cells control the peripheral TCR repertoire during the course of immune responses to both self and foreign antigens.

Journal

Annual Review of Immunology – Annual Reviews

Published: Apr 1, 2000

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