The specific regulation of immune responses by CD8+ T cells restricted by the MHC class Ib molecule, Qa-1.
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.
Jiang
H
H
Department of Medicine and Pathology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Chess
L
L
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D006183:H-2 Antigens / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins / Q000276:immunology; D051920:NK Cell Lectin-Like Receptor Subfamily D; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*
D015703:Antigens, CD; D006183:H-2 Antigens; D015395:Histocompatibility Antigens Class I; C497869:KLRD1 protein, human; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D051920:NK Cell Lectin-Like Receptor Subfamily D; C032907:Q surface antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta