The outer surface lipoprotein A of Borrelia burgdorferi provides direct and indirect augmenting/co-stimulatory signals for the activation of CD4+ and CD8+ T cells.
Naive CD4+ and CD8+ T cells require two distinct signals to proliferate and to express effector functions [1]. One is provided by the antigen receptor on the T cell (TCR) after its encounter with antigenic peptides associated with class I or II major histocompatibility complex (MHC) molecules on antigen-presenting cells (APC) [2]. The second signal, which is not antigen-specific but essential for proliferation and differentiation of naive T cells, is provided by co-stimulatory structures. The major co-stimulatory molecules for CD4+ T cells seem to be B7 [3], B7.2 [4,5], and heat-stable antigen (HSA) [6]. These molecules are expressed on a variety of naive and/or activated APC and bind to CD28 and CTLA-4 and possibly other, as yet undefined, TCRs [3,7]. Optimal T cell activation only occurs when co-stimulatory molecules and ligands for the TCR are expressed on the same APC [8,9]. However, co-stimulation for T cells may also be provided via bystander cells [8,9] or by glycoproteins of the extracellular matrix, like fibronectin [10] and laminin [11]. In this case, T-cell VLA integrins function as signaling molecules [10,11]. This indicates that antigen-specific T-cell activation may also occur in areas where antigens are presented in association with extracellular matrix proteins. The recent finding that the invasion protein of Yersinia spp. delivers co-stimulatory signals to anti-CD3-activated human T cells, most probably through the b1 integrins, suggests that bacterial products can also bind to contribute to the activation of T cells [12].(ABSTRACT TRUNCATED AT 250 WORDS)
Simon
M M
MM
Max-Planck-Institut für Immunbiologie, Freiburg, Germany.
Nerz
G
G
Kramer
M D
MD
Hurtenbach
U
U
Schaible
U E
UE
Wallich
R
R
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D001428:Bacterial Vaccines; D015748:Borrelia burgdorferi Group / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D008074:Lipoproteins; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D016853:Muromonab-CD3 / Q000494:pharmacology; D015398:Signal Transduction
D000942:Antigens, Bacterial; D000954:Antigens, Surface; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D017252:CD3 Complex; D008074:Lipoproteins; D016853:Muromonab-CD3; C072045:OspA protein